• Volume 29,Issue 5,2021 Table of Contents
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    • Study of a model of autoimmune premature ovarian failure

      2021, 29(5):563-569. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 001

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      Abstract: Objective To improve a mouse model of autoimmune premature ovarian failure, different modeling times and adjuvant were used to determine factors related to induction of premature ovarian failure by zona pellucida glycoprotein 3 (ZP3). Methods B6AF1 mice with regular estrous cycles were randomly divided into five groups: normal, model A, model B, model C and model D groups. At the end of the experiment, serum was collected to detect sex hormones, and ovaries were collected to observe pathological changes, including effects on the zona pellucida and apoptosis of ovarian cells. Results Compared with the normal group, the model B, C and D groups showed estrous cycle disorders, including high gonadotropin and low estrogen levels, increased follicle atresia, obvious zona pellucida and increased apoptosis of ovarian apoptotic cells. The model C and model D groups had more obvious changes in the number of atretic follicles, ovarian apoptotic cells and zona pellucida. Conclusions In ZP3 induced autoimmune premature ovarian failure, the two-component model with three times immunization produced a stronger effect, and the modeling rate was 80%, which can be used as a reference for future modeling.

    • Experimental study on the adhesion and antioxidant effect of MAP on ulcerative colitis in rats

      2021, 29(5):570-577. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 002

      Abstract (2308) HTML (0) PDF 7.42 M (1873) Comment (0) Favorites

      Abstract: Objective To observe the effect of mussel adhesive protein(MAP) on the intestinal mucosa of rats with ulcerative colitis, and to explore potential mechanisms from the perspectives of adhesion and antioxidant actions. Methods A total of 32 specific pathogen-free grade SD rats were randomly divided into four groups: a normal group, model group, mesalazine group and MAP group (0. 6 mg / kg body weight), with eight rats in each group. The normal group was provided ordinary drinking water, whereas the other groups were given 5% dextran sodium sulfate (DSS) for 7 days to induce ulcerative colitis, and daily dosing was started during the 24 h after molding. The disease activity index (DAI) scores and body weights of the rats in each group were observed and recorded. After 7 days of DSS administration, samples were collected to determine the colorectal length and intestine:body weight ratio for each group, and the histology and gross morphology of the colorectal mucosa were examined. The adhesion and antioxidant effects of MAP on the intestinal mucosa of rats was investigated in vitro by nitro blue tetrazolium chloride (NBT) staining. Results Compared with the normal group, the model group showed significantly higher DAI scores (P< 0. 05) and a decreased body weight (P< 0. 05) from day 5 onwards, and shorter colorectal length and lower intestinal weight ratio (P< 0. 05), as well as higher colon mucosal damage index (CMDI) (P< 0. 05) and pathohistological (P< 0.05) scores. Congestion, edema, and ulceration were observed in the colorectal mucosa, as well as swelling and distortion of the colonic crypts and extensive infiltration of inflammatory cells in submucosal tissue. These findings showed that the ulcerative colitis model was successfully established in rats. Compared with the model group, the body weight and colorectal length of rats in the mesalazine and MAP groups were increased (P< 0. 05), whereas DAI scores, intestinal weight ratio, and CMDI and histopathological scores were decreased (P< 0. 05). In comparison with the mesalazine group, rats in the MAP group showed similar body weight growth trends and DAI scores, as well as similar levels of intestinal mucosal edema, congestion and inflammatory cell infiltration, indicating that MAP had potentially similar therapeutic effects to those of mesalazine in ulcerative colitis. The NBT staining produced blue histology in the rectal mucosa of rats, and the degree of blue staining increased with time. Conclusions Through adhesion and antioxidant effects on intestinal mucosa, MAP can significantly improve the symptoms of dilute stool, blood in stool and weight loss in rats with ulcerative colitis, and repair a damaged intestinal mucosal barrier. Additionally, MAP reduced the congestion and edema of rat rectal mucosa, as well as effectively reduced the infiltration of inflammatory cells, suggesting therapeutic potential for the treatment of ulcerative colitis by MAP.

    • Changes in spinal A1 astrocyte polarization during peripheral inflammatory pain

      2021, 29(5):578-584. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 003

      Abstract (1909) HTML (0) PDF 9.57 M (1745) Comment (0) Favorites

      Abstract: Objective Chronic inflammatory pain is a common disease that severely disrupts the quality of life of patients. The latest research shows that reactive astrocytes can be polarized to two different phenotypes, A1 and A2 astrocytes. Type A1 astrocytes can secrete pro-inflammatory cytokines and promote neuroinflammation, and type A2 astrocytes can secrete neurotrophic factors and promote tissue repair. This paper aimed to study pain behavior and changes to A1 astrocytes in the spinal cord of mice with peripheral inflammatory pain, to elucidate the pathological mechanisms of peripheral inflammatory pain. Methods A total of 16 male C57BL/ 6 mice were divided into the control group and inflammatory pain group (eight mice per group). The inflammatory pain model was established by injection of complete Freund′s adjuvant (CFA) into the plantar surface of the right hind paw. The control group were injected with an equivalent volume of saline. The mechanical withdrawal threshold (MWT) and the radiant heat stimulating paw withdrawal latency (PWL) of mice were measured before and 1, 3, 5 and 7 days after the CFA injection. Reverse transcription polymerase chain reaction was used to detect the expression of A1 and A2 astrocyte markers. Immunohistochemistry was used to detect the expression of glial fibrillary acidic protein ( GFAP) in the spinal dorsal horn to identify the process of astrocyte activation. Finally, the co-localization of A1 astrocyte marker C3 and GFAP in the spinal dorsal horn was detected. Results The ipsilateral MWT and PWL had both significantly decreased after CFA injection, indicating that the mice developed mechanical hyperalgesia and thermal hyperalgesia. At the third day after CFA injection, the expression levels of spinal GFAP were significantly increased compared to the day 0 (D0) group (1. 84 ± 0. 10 vs. 1. 08 ± 0. 22, respectively, P< 0. 05). On the 7th day after CFA injection, the mRNA levels of A1 astrocyte markers Serping1 and Lcn2 were increased vs. the D0 group (P<0. 05), and mRNA levels of A2 astrocyte markers S100a10 and Ptx3 were decreased vs. the D0 group (P<0. 05). The co-expression of C3 and GFAP in the spinal dorsal horn was increased in the CFA vs. D0 group (P<0. 05). Conclusions The reactive astrocytes in the spinal dorsal horn of mice with inflammatory pain were polarized to type A1, suggesting that A1 astrocytes may be involved in the development of inflammatory pain.

    • Therapeutic effects of oltipraz on the pain and inflammation responses of a mouse model of acute gouty arthritis and related mechanisms

      2021, 29(5):585-592. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 004

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      Abstract: Objective To establish a mouse model of acute gouty arthritis (AGA), and to study whether oltipraz can improve the joint inflammation and pain in this model. Methods Healthy male C57 / BL6 mice were randomly divided into control, MSU+Vehicle (MSU+Veh), MSU+Oltipraz high-dose (MSU+100 mg / kg oltipraz), MSU+Oltipraz low-dose (MSU+30 mg / kg oltipraz), and MSU+Indomethacin (MSU+Indo) groups. Mice of the control group were injected with phosphate buffered saline, whereas the other groups were injected with monosodium urate (MSU) in the right ankle to establish AGA. After the establishment of AGA, the MSU+Oltipraz group was intraperitoneally injected with oltipraz, the MSU+Indo group was intraperitoneally injected with indomethacin at the same time point, and mice in the other groups were intraperitoneally injected with the same volume of vehicle. Calipers were used to measure ankle joint swelling before and after model establishment and treatments. The 50% mechanical paw withdrawal threshold ( 50% PWT) of mice was measured by the von Frey method . Pathological changes of ankle synovial tissues were evaluated. The DigiGait imaging system was used to measure the gait of mice and changes of gait behavior before and after model establishment. An oxidative molecular detection kit was used to detect the oxidative stress-related molecules in mouse ankle joints. The expression levels of inflammatory factors in ankle joints were examined by qPCR. Results Compared with the control group, the MSU group had obvious ankle joint swelling and the 50% PWT was significantly reduced (P<0. 01). Pathological analysis indicated that the synovial tissues of the ankle joint showed extensive inflammatory cell infiltration in the MSU group compared with the control group (P<0. 05). Gait analysis showed that the stride length of hind limb was significantly shortened, and the paw area was significantly reduced (P<0. 01) in the MSU group compared with the control group. Compared with the MSU +Veh group, the 50% PWT of the ipsilateral side of mice in the MSU+100 mg / kg oltipraz group was significantly increased (P<0. 01), the ankle joint swelling was greatly reduced and gait parameters were markedly improved (P<0. 05), the level of oxidative stress in ankle joints was significantly decreased (P<0. 05), and the expression levels of inflammatory cytokine IL-1β and TNF-α mRNAs were dramatically decreased in the MSU+100 mg / kg oltipraz group compared with the MSU+Veh group ( P< 0. 01), an effect similar to that of indomethacin, whereas 30 mg / kg oltipraz had no significant effect. Conclusions Oltipraz can alleviate ankle joint swelling and mechanical hyperalgesia in the AGA mouse model. This therapeutic effect is probably related to reduced oxidative stress and inflammatory cytokine levels, and the increased expression of antioxidant substances in the ankle tissue of AGA mice by oltipraz treatment.

    • Role of upregulated P2X3 expression in dorsal root ganglia during diabetic neuropathic pain

      2021, 29(5):593-599. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 005

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      Abstract: Objective To observe the expression of purinergic receptor subtype P2X3 ( P2X3) in dorsal root ganglion (DRG) of rats at different stages after injection of streptozotocin ( STZ), and the intervention effect of P2X3 receptor antagonist TNP-ATP in diabetic neuralgia (DNP) rats. Methods ( 1) Six of 20 healthy male SD rats were randomly selected as the normal group, and the other 14 rats were intraperitoneally injected with STZ. Two STZ treated rats without modeling were excluded. The paw withdrawal threshold (PWT) was observed before and 7, 14 and 21 days after modeling. The L4-L6 DRG of rats were collected at the above time points, and the expression of P2X3 positive cells was detected by immunofluorescence. (2) Six of 25 healthy male SD rats were randomly selected as the normal + normal saline (Control + NS) group, and the remaining 19 rats were injected with STZ. One STZ injected rat was excluded. The rats with successfully established DNP were randomly divided into a model + normal saline (DNP + NS) group, model + 50 nmol P2X3 inhibitor TNP-ATP (DNP + 50 nmol TNP-ATP) group, and model + 100 nmol P2X3 inhibitor TNP-ATP (DNP + 100 nmol TNP-ATP) group, with six rats in each group. Fourteen days after STZ injection, the DNP + TNP-ATP group was injected with 100 nmol TNP-ATP solution in the dorsum of the foot, whereas the other two groups were injected with the same volume of NS, and the PWT was observed at 0. 5, 1 and 1. 5 h after injection. The effect of drug injection on PWT was also observed after 7 days. Results (1) Compared with the normal group, fasting blood glucose was significantly increased in rats of the model group on Day 7, Day 14 and Day 21. Compared with the normal group, there was no significant change in the PWT of the model group at Day 7, but there was a significant decrease in PWT at Day 14 and Day 21. Immunofluorescence showed that the expression of P2X3 positive cells on L4 and L5 DRG from the DNP group was significantly increased 7, 14 and 21 days after STZ injection compared with the normal group. (2) Before TNP-ATP intervention, there were no significant differences in the PWT between the DNP + NS, DNP + 50 nmol TNP-ATP and DNP + 100 nmol TNP-ATP groups. Compared with DNP + NS and DNP + 50 nmol TNP-ATP groups, the PWT in the DNP + 100 nmol TNP-ATP group was significantly increased after 0. 5 h intervention, and the effect lasted for 1 h. (3) After continuous injection of TNP-ATP for 7 days, the PWT in the DNP + 100 nmol TNP-ATP group was significantly higher than that in DNP + NS and DNP + 50 nmol TNP-ATP groups. Conclusions The DNP rat model was successfully established by intraperitoneal injection of STZ, and up-regulation of P2X3 expression in the DRG may be involved in the regulation of diabetic neuralgia.

    • Intervention effect of chitosan on acute lung injury induced by PM2.5 in mice

      2021, 29(5):600-605. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 006

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      Abstract: Objective To explore the intervention effect of chitosan on acute lung injury induced by particulate matter with a diameter ≤ 2.5 μm (PM2.5 ) in mice. Methods Forty-four specific pathogen-free male C57BL/ 6J mice were randomly divided into four groups: control, PM2.5 , chitosan and chitosan+PM2. 5 groups. Animals from the chitosan+ PM2.5 and chitosan groups were intragastrically administered chitosan daily for 2 weeks, and animals from the control and PM2.5 exposure groups were intragastrically administered distilled water once a day. After 2 weeks, the PM2.5 group was exposed to PM2.5 ( 4 mg / kg BW) via intratracheal instillation, whereas the control and chitosan groups were exposed to tracheal inhalation of normal saline, daily for 1 week. Animals were examined 24 h after the last exposure. Hematoxylin- eosin (HE) staining was used for morphological observation. The levels of malondialdehyde (MDA), total protein (TP) and lactate dehydrogenase ( LDH ) in alveolar lavage fluid ( BALF ) and liver samples were determined by spectrophotometry. The expression of interleukin-1β (IL-1β), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) in BALF and serum were determined by ELISA. Results HE staining showed that the alveolar septum was significantly widened in PM2.5 group, and there was obvious infiltration of lymphoid and plasma cells. The lung septum was markedly narrowed in the chitosan + PM2.5 group compared with the PM2.5 group, and infiltration of lymph and plasma cells was.

    • Effects of aerobic and anaerobic FMT preparation on fecal microbiota and metabolite profiles in swine

      2021, 29(5):606-617. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 007

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      Abstract: Objective Fecal microbiota transplantation (FMT) is a promising, but immature intervention in the current pig production. The aim of this study was to investigate the effects of aerobic and anaerobic FMT preparation (T1 group and T2 group, respectively) on fecal microbiota and metabolite profiles of SPF Bama mini pigs. Methods Amplicon sequencing and untargeted metabolomics method were used to reveal the effects of aerobic and anaerobic FMT preparation (T1 group and T2 group, respectively) on fecal microbiota and metabolite profiles of SPF Bama mini pigs. Results (1) The two FMT preparation method preserved all the bacterial phyla in untreated pig slurries ( C group). Firmicutes and Bacteroidetes constituted the top two phyla in the gut microbiota in all groups, and FMT preparation result ed in a significant decrease of Treponema bacteria. (2) In untreated pig slurries, the two most abundant fungal phyla were Ascomycota and Basidionmycota. FMT preparation significantly increased the relative abundance of Ascomycota, and aerobic FMT preparation removed the Wallemia genus. These changes in microbial community did not affect the functional contributions.(3) A total of 402 and 195 characteristic metabolites were respectively detected by positive and negative mode liquid chromatograohy-mass spectrometry, including Lipids and lipid molecules, and Organoheterocyclic compounds. Disturbance of amino acid metabolism, and lipid metabolism were the most significant in T1 versus C comparison, and T2 versus C comparison, 155 and 201 confirmed differential metabolites using reference compounds were identified, respectively. Highly positive correlated metabolites with Spearman correlation coefficient r> 0. 6 are connected with Trepronema_2 in T1 versus C and T2 versus C comparisons, and highly negative correlated metabolites with r< - 0. 4 are connected with Ruminococcaceae_ NK4A214 group in T1 versus C and T2 versus C comparisons. Conclusions Although the FMT preparation time is short, the effect of short aerobic exposure on the abundance of fungal communities in the samples was higher than that of short anaerobic exposure, and the relative abundance of harmful bacteria such as Treponema and Spirochaetes and related metabolites were effectively reduced, which could improve the safety of FMT.

    • Protective effect and mechanism of regular aerobic exercise on cerebral ischemia in rats

      2021, 29(5):618-625. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 008

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      Abstract: Objective To investigate the protective effect and mechanism of regular aerobic exercise on cerebral ischemia in rats. Methods According to the random number table method , 40 specific pathogen-free male SD rats were randomly divided into sham operation, model, experimental, and control groups. The middle cerebral artery occlusion (MCAO) rat model was constructed by the thread plug method . Rats in the sham operation group were threaded without ligation. Rats in the experimental group performed regular aerobic exercise ( running on a treadmill) every day with an exercise intensity of 20 m/ min, three times a day, 20 min each time, and 2 h apart each time. Rats in the control group were given 1. 08 mg / mL nimodipine by gavage daily. Laser speckle imaging was used to observe changes in blood flow in the cerebral cortex. Electroencephalograms were used to detect changes in total power in the cerebral cortex. 2, 3, 5- triphenyltetrazolium chloride staining was used to detect cerebral infarct areas. Western Blot was used to detect the expression of brain-derived neurotrophic factor ( BDNF) and growth-associated protein 43 ( GAP43) in brain tissue. Results Compared with the sham group, the cerebral cortex blood perfusion, total cerebral cortex power, and expression of BDNF and GAP43 in the model, experimental, and control groups were significantly decreased (P<0.05), and infarct area was significantly increased (P< 0. 05). Compared with the model group, the cerebral cortex blood perfusion, total cerebral cortex power, and expression of BDNF and GAP43 in the experimental and control groups were significantly increased (P<0. 05), and the infarct area was significantly decreased (P<0. 05). Conclusions Regular aerobic exercise can significantly improve blood perfusion and cerebral microvascular circulatory disorders in cerebral ischemic rats, reduce infarct size in brain tissue, and inhibit the inflammatory cascade, which may be related to activation of the BDNF/ GAP43 pathway.

    • Comparative study of steroid hormone synthesis in a drug-induced deficiency syndrome by continuous and interval administration of cisplatin in mice

      2021, 29(5):626-636. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 009

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      Abstract: Objective To research the effect of different administration protocols of cisplatin on the biosynthesis and reserve of steroids in mice. Methods Forty female ICR mice were randomly divided into four groups: a cisplatin continuous administration group (CA-group), a cisplatin interval administration group (IA-group), and two corresponding control groups. The CA-group was injected with 3 mg / kg cisplatin for 7 consecutive days. The IA-group was injected with 10 mg / kg cisplatin once per week, for 4 weeks. Rotating-stick, holding power, movements and axillary temperature were examined before the last injection, also the end of laboratory animal model making. The day after, the mice were killed, the visceral organs were separated weighed, included the kidney, heart, thymus and spleen. Relative mRNA expression levels in the hypothalamus (GnRH and CRH), pituitary (Pomc, Fshb, Lhb, and Pou1f1), adrenal and ovary (StAR, Cyp11a1, Cyp21a1, Cyp17a1, Cyp11b1, Hsd3b2, Cyp19a1, Hsd17b1, Esr1, Esr2, and Gper1) tissue were examined by RT-qPCR. Protein expression levels ( StAR, CYP11A1, CYP21A2 and CYP11B1) in adrenal and ovary tissues were examined. Results Compared with the control group, body weight was reduced by cisplatin in two different mouse models. Visceral organs were inhibited and the Qi deficiency syndrome was induced by cisplatin administration. In two different cisplatin models, murine primordial follicles showed accelerated activation and differentiation, and many atretic follicles were produced containing apoptotic granulosa and theca cells. Healthy mature follicle numbers were reduced significantly. There were no detectable changes in adrenal histology. In adrenal tissue, StAR expression was inhibited in the CA-group and upregulated in the IA-group, which also exhibited reduced CYP11B1 protein expression. In the ovary, the expression levels of Cyp11a1, Hsd3b2, Esr1, and Gper1 mRNAs were upregulated and Star and Cyp17a1 mRNA expression was reduced in the CA-group. The expression levels of StAR protein and Hsd3b2 mRNA were decreased in the IA-group. In the hypothalamus, the expression levels of GnRH and CRH mRNAs were reduced in the CA-group. In the pituitary, the expression levels of Pomc, Fshb and Pou1f1 mRNAs were increased in the CA-group, and level of Lhb mRNA was reduced in the IA-group. Conclusions Qi deficiency syndrome and vital essence deficiency syndrome in mice can be induced by cisplatin. The ovary was damaged more significantly and selectivity than the adrenal gland. The functions of the hypothalamus and pituitary were further inhibited by continuous cisplatin injection in the short-term.

    • Effects of 8 weeks’ aerobic exercise on the skeletal muscle inflammation and exercise ability of obese mice

      2021, 29(5):637-643. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 010

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      Abstract:We aimed to determine the effects of 8 weeks of aerobic exercise on obesity in mice induced by high-fat diet-feeding and the mechanisms involved. Forty-six male C57BL/ 6 mice were randomly allocated to a normal diet group and high-fat diet group, then to a Control Sedentary group (CS group), a Control Exercise group (CE group), an Obese Sedentary group (OS group), and an Obese Exercise group (OE group). The exercise groups underwent moderate-intensity aerobic exercise at 60% of maximum exercise intensity for 8 weeks. Before and after this exercise intervention, the maximum exercise ability of each group was determined, and the dietary energy intake and body mass of the mice were measured regularly during the intervention. The mice were euthanized and both gastrocnemius muscles were removed 48 hours after the last exercise bout. The desmin distribution in the muscles was assessed following immunofluorescence staining, and the cross-sectional area and inflammatory cell infiltration in skeletal muscle were assessed following hematoxylin and eosin staining. Western Blot was used to measure the expression of proteins related to atrophy and inflammation in skeletal muscle. The energy intake, body mass, and expression of atrogin-1, muscle ring finger (MuRF1), and tumor necrosis factor (TNF) -α protein was significantly higher in the OS group than in the CS group (P< 0.05); whereas the exercise ability, cross-sectional area of muscle fibers, and interleukin ( IL) - 10 protein expression were significantly lower (P< 0.05). In addition, desmin protein expression was disordered. After aerobic exercise, there was no significant difference in energy intake between the OS and OE groups. However, the body mass and protein expression of atrogin-1, MuRF1, TNF-α, and IL-1β were significantly lower in the OS group (P< 0.05) and the exercise ability, cross- sectional area of muscle fibers, and IL-10 protein expression were significantly higher (P< 0.05). In addition, the protein expression of atrogin-1, MuRF1, TNF-α, and IL-1β in the CE group was significantly lower than in the CS group (P< 0.01), whereas the IL-10 protein expression was significantly higher (P< 0.05). In conclusion, high-fat diet-induced obesity is associated with chronic inflammation in skeletal muscle, which leads to skeletal muscle atrophy and a decline in exercise capacity. Conversely, aerobic exercise ameliorates this skeletal muscle atrophy, which improves exercise ability, and a reduction in local inflammation may play a key role in this effect.

    • Construction and evaluation of two obese rat models of polycystic ovary syndrome with insulin resistance

      2021, 29(5):644-650. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 011

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      Abstract: Objective To establish an animal model of obese polycystic ovary syndrome combined with insulin resistance ( PCOS-IR) using two different method with a high-fat diet, and to compare the changes in endocrine and metabolic characteristics. Methods Rats were randomly divided into a control group (ordinary feed and purified water), a letrozole group (intragastric administration of 1 mg / kg), and a human chorionic gonadotropin + insulin (HCG+INS) group (subcutaneous injections). The latter two groups were fed a high-fat diet and 5% glucose solution. Gram staining was used to observe two estrous cycles. On the 23rd and 30th day, ovarian and uterine wet weights were measured. Hematoxylin-eosin staining was used to observe ovarian histopathology. Fasting blood glucose (FBG), and blood levels of triglyceride (TG) and total cholesterol (TC) were measured by a biochemical analyzer. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone ( LH), estradiol ( E2), total testosterone ( T), and inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β ( IL-1β) were measured by enzyme-linked immunosorbent assays. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Real-time fluorescence quantitative PCR was used to detect ovarian TNF-α and IL-1β mRNA levels. Results The letrozole and HCG+INS groups both had disordered estrous cycles compared with the control group, but the HCG+INS group had occasional ovulation. On the 23rd day, uterine weight and E2 levels were significantly reduced, and ovarian weight, INS, HOMA-IR, TG, and T levels were significantly increased in the letrozole group compared with controls. In the HCG+INS group, INS, HOMA-IR, TC, TG, and LH levels were significantly increased, and E2 levels were significantly reduced compared with controls. On the 30th day, the levels of FBG, INS, HOMA-IR, TG, FSH, LH, serum TNF-α and IL-1β, and ovarian TNF-α and IL-1β mRNA levels were significantly increased in the letrozole and HCG + INS groups versus the control group. The letrozole group exhibited anovulation, hyperandrogenism, and obesity, as well as more obvious pathological changes consistent with polycystic ovaries. Conclusions Both approaches successfully induced the PCOS-IR animal model. The changes in body weight, and endocrine and metabolic indexes of the letrozole model on the 30th day were more consistent with the pathological characteristics of obese PCOS-IR.

    • Establishment and evaluation of orthotopic transplantation model of human glioma in miniature pigs

      2021, 29(5):651-656. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 012

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      Abstract: Objective To establish an orthotopic xenograft model of human glioma miniature pigs by treatment with immunosuppressive agents, and provide ideal experimental tools for screening glioma drug and imaging studies. Methods Human glioma cells U87-MG were transplanted into nude mice subcutaneously, and tumors were visible after two weeks. Then, we choose miniature pigs to be treated with oral immunosuppressant both cyclosporine soft capsules (20 mg / kg) and tacrolimus capsules ( 0. 01 mg / kg). Three days later, the fresh tumor tissue derived from nude mice were collected and trim them into 1 mm3 tissue pieces. The tumor tissue were transplanted into cerebral striatum of the miniature pigs treated with immunosuppressive agents through a stereotactic instrument. After 21 days of continuous use of immunosuppressive agents, the animals displayed obviously thin, and space-occupying lesions in the brain were detected by Magnetic Resonance Imaging(MRI)to confirm tumors formation. These miniature pigs were sacrificed and dissected, then the tumor tissues were fixed. The histomorphological characteristics of tumor were confirmed by H&E and IHC staining. Results Three weeks after orthotopic transplantation of the glioma tissue into the brain striatum of miniature pigs, 12 pigs have been implanted with U87-MG, 11 have presented a macroscopic significant tumor, with radiological and pathological characteristics of high-grade glioma. we found that the tumor incidence reached more than 90% by MRI scan. Both the HE staining result and growth characteristics of the tissue were consistent with tumor characteristics. The staining of human mitochondrial antibody demonstrated that this tumor was human-derived tissue and the glioma-specific marker GFAP was expressed positively. Conclusions Combined with cyclosporine soft capsule and tacrolimus immunosuppressive treatment, an orthotopic xenograft miniature pig model of human glioma was successfully established by transplanting tumor tissue.

    • Establishment of a peri-prosthetic infection model after total knee arthroplasty in New Zealand rabbits

      2021, 29(5):657-663. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 013

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      Abstract: Objective To explore the method and feasibility of establishing a peri-prosthetic infection model after total knee arthroplasty in New Zealand rabbits. Methods Forty-eight healthy New Zealand rabbits were randomly divided into three groups: an experimental group ( peri-prosthetic infection group), a control group ( non-peri-prosthetic infection group), and a blank control group (sham surgery group). A bacterial suspension of Staphylococcus aureus (0. 5 mL, 1 × 107 CFU/ mL) was injected into the joint cavity of New Zealand rabbits 7 d after total knee arthroplasty in the experimental group, while 0. 5 mL saline was injected into the joint cavity of New Zealand rabbits 7 d after the total knee arthroplasty in the control group, and no treatment was undertaken after the capsule incision and suture of the knee joint in the blank control group. Hematology examination was performed 1 day before surgery and 7, 14, and 21 d after surgery in each group. X-ray examination, bacteriology, and pathology examination were performed 21 d after surgery. Results The survival rate of the experimental group was 87. 5% ( 14 / 16), and that of the control group and the blank control group was 100%. Twenty-one days after surgery, X-ray examination showed that the prosthesis was good in the experimental group and the control group, and there was no loosening around the prosthesis. The soft tissue around the joint was swollen in the experimental group, but not in the control group and the blank control group. Hematology examination showed that WBC, ESR, and CRP were significantly higher in the experimental group than in the control and blank control groups ( P< 0. 05). The bacteriological examination showed that the bacterial culture was positive in the experimental group, and the infection rate was 100% (14 / 14), while the infection rate was 6. 3% (1 / 16) in one case in the control group, and the bacterial culture was negative in the blank control group, with an infection rate of 0% (0 / 16). Pathological examination showed that there was a large amount of inflammatory cell infiltration around the prosthesis in the experimental group. Conversely, there was no inflammatory cell infiltration around the prosthesis in the control group and blank control group. Conclusions Injection of 0. 5 mL Staphylococcus aureus into the joint cavity 7 days after total knee arthroplasty in New Zealand rabbits was successfully established as a peri-prosthetic infection model after total knee arthroplasty.

    • Effect of curcumin on hepatic 11β-HSD1 expression and insulin resistance in rats with nonalcoholic fatty liver disease

      2021, 29(5):664-669. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 014

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      Abstract: Objective To observe the effect of curcumin on hepatic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression and insulin resistance in rats with nonalcoholic fatty liver disease (NAFLD). Methods Thirty- two male Wistar rats were randomly divided into four groups: control, NAFLD model, low-dosage curcumin treatment (C1) and high-dosage curcumin treatment (C2) groups. The NAFLD model was established by a high-fat / high-sugar diet. After 8 weeks of the diet, the C1 and C2 groups were given 200 and 400 mg / ( kg·d) curcumin, respectively, by intragastric administration for 8 weeks. Results Compared with the model group, the NAFLD was significantly improved in the C1 and C2 groups, expressed as the reduction of the fatty liver index, serum lipids, liver lipid deposition, improvement of liver function and pathological changes. Insulin resistance was also significantly improved. The relative expression levels of 11β- HSD1 mRNA and protein in liver tissue were significantly lower in the C1 ( 0. 157 ± 0. 013 and 0. 264 ± 0. 062, respectively) and C2 groups (0. 091 ± 0. 009 and 0. 191 ± 0. 021, respectively) than those in the model group (0. 264 ± 0. 015 and 0. 477 ± 0. 074, respectively) (P< 0.05, P< 0.01). All curcumin treatment effects were dose-dependent. Conclusions Curcumin significantly improved NAFLD in rats, and this effect may be related to the inhibition of 11β- HSD1 expression and the improvement of insulin resistance.

    • Progress in research into transmissible spongiform encephalopathies using Drosophila models

      2021, 29(5):670-674. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 015

      Abstract (1612) HTML (0) PDF 800.70 K (1578) Comment (0) Favorites

      Abstract:Transmissible spongiform encephalopathies, or prion diseases, are a group of fatal neurodegenerative illnesses that affect humans and other mammalian species. All forms of prion disease are associated with misfolding of the host-encoded prion protein, PrPC , into one of several pathogenic isoforms, collectively termed PrPSc . The current bioassays for prions typically involve intracerebral or peripheral inoculation of test material into an experimental host and subsequent euthanasia when clinical signs of terminal prion disease become evident. Consequently, bioassays of prion infectivity invertebrate species are cumbersome, time-consuming, expensive, and increasingly open to ethical dispute because the test animals are subjected to terminal neurodegenerative disease. Here, we discuss the development of a Drosophila-based prion bioassay, a highly sensitive and rapid invertebrate in vivo assay that efficiently identifies mammalian prions and permits the reduction and replacement of sentient experimental animals. This article provides an overview of the method ology involved in the model and discusses the experimental data that describe its viability and usefulness in place of more sentient species.

    • Role and signaling pathway of Caveolin-1 in aging

      2021, 29(5):675-680. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 016

      Abstract (1743) HTML (0) PDF 1.86 M (2250) Comment (0) Favorites

      Abstract:Aging is an inevitable process in organisms that proceeds spontaneously over time and leads to the development of aging-related diseases. The increase of senile diseases adds to the medical burden of society. Therefore, an important research direction in aging biology is to find therapeutic targets for aging-related diseases. Caveolin-1 (Cav-1) is an important structural protein of caveolin, which is involved in many cellular processes, such as signaling transduction, cholesterol balance, migration and aging. Numerous studies have shown that Cav-1 plays an important role in mediating and regulating aging. This article reviews the role and signaling pathways of Cav-1 in aging and potential therapeutic targets for aging and aging-related diseases.

    • Research progress of animal model of diabetic retinopathy

      2021, 29(5):681-688. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 017

      Abstract (2274) HTML (0) PDF 866.08 K (4300) Comment (0) Favorites

      Abstract:Diabetic retinopathy is the main cause of low vision and blindness in adults, and its pathogenesis is complex. Animal models can help us to understand the pathogenesis of diseases more comprehensively. A reasonable animal model is the key to explore the pathogenesis of diseases. According to the clinical manifestations of diabetic retinopathy, drug-induced, high-fat and high-sugar diet and genetic animal models were introduced in this paper. In addition, the pathological characteristics of animal models of diabetic retinopathy induced by different method were briefly summarized in order to provide reference for the research on the mechanism of diabetic retinopathy and the corresponding drug development.

    • Research progress of brain morphology and function in naked mole-rats and application prospects

      2021, 29(5):689-694. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 018

      Abstract (1734) HTML (0) PDF 802.45 K (1665) Comment (0) Favorites

      Abstract:Recently, naked mole-rats have become increasingly used in scientific research because of their advantages in anti-tumor, anti-hypoxia, anti-pain and long life-span studies. In this article, we summarize the brain morphology of naked mole-rats, and systematically describe the central structures of the brain that control the functions of vision, hearing, olfactory sense and sensation, and the adaptation of naked mole-rats to low oxygen, darkness and other underground environments. The naked mole rat is expected to become a dominant animal model for the study of neurodegenerative diseases and other aspects of neurological disorders, and may promote the development of medicines for human neurological health in the future.

    • Progress in the use of Chinese miniature pigs in biomedical research

      2021, 29(5):695-706. DOI: 10. 3969 / j.issn.1005-4847. 2021. 05. 019

      Abstract (2193) HTML (0) PDF 1.00 M (3768) Comment (0) Favorites

      Abstract:Miniature pigs are similar to humans in terms of their physiology, anatomy, nutrition, metabolism, drug metabolism, and disease development and are therefore widely used in the study of human disease. Chinese miniature pigs have stable genetics but are also outbred. However, the harnessing of the characteristics of Chinese miniature pigs in the establishment of mini-pig models of human disease that meet the needs of biomedical research is still in the exploratory stage. In this article, we summarize the status of the breeds of Chinese miniature pig with respect to research into human diseases in order to provide a reference and guidance for the further use of this species in the study of human diseases.

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