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YU Xuan , LI Xianglei , SUN Xiuping , QIN Chuan
2021, 29(6):707-714. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 001
Abstract: Objective This research investigated the expression of REST in repeated corticosterone injected mice and the effects of REST on depression- and anxiety-like behaviors in model mice. Methods A chronic stress mouse model was established by repeated subcutaneous injections of corticosterone. An AAV virus vector overexpressing REST was injected into the hippocampus of the mouse brain. Then, the depression- and anxiety-like behaviors of mice were assessed by several behavioral tests. Finally, we detected the expression of REST-related genes by real-time RT-PCR. Results Repeated subcutaneous injections of corticosterone for 4 weeks successfully induced depression-like behavior and reduced body weight in mice (P< 0.01). REST overexpression in the hippocampus influenced the performance of model mice in the depression and anxiety behavioral tests. Specifically, it reduced the immobility time of model mice in the tail suspension test and forced swimming test and the number of entries into the central area in the open field test. In addition, REST overexpression increased the exploration frequency and residence time in the enclosed arms of the elevated cross maze. The RNA transcription levels of Bndf, Nt3, Ngf and Fgf2 were also affected in model mice after REST overexpression. Conclusions REST plays a bidirectional role in the corticosterone-induced depression mouse model. Its mechanism may be related to its participation in the regulation of multiple target genes and the comprehensive effect of different signaling pathways.
YANG Jubeng , ZHAO Xianfang , NIE Falong , XIAO Chun , DAI Rong , LI Xiufang
2021, 29(6):715-723. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 002
Abstract: Objective To explore the effect of cold-warm cycle stimulation on nasal mucosal immune barrier function in rats and determine the difference between Mahuang decoction and Yinqiao powder, which are commonly used in traditional Chinese medicine. Methods For cold-warm cycle stimulation, SD rats were exposed to four cycles of -15°C for 1 hour and then 25°C for 30 minutes. At different time points after the last stimulation, the protein expression of IgA in the nasal mucosa was detected by Western blot. Seven days after the first cold-warm cycle stimulation, the rats were re- subjected to cold-warm cycle stimulation under the same conditions. The dynamic changes in IgA protein expression in the nasal mucosa, lysozyme and prostaglandin E2 (PGE2) levels in nasal lavage fluid and PGE2, TNF-α, IL-6 and IL-1β serum contents were detected on days 1 ~ 11 after the last stimulation. The rats were randomly divided into negative control, model, Mahuang decoction and Yinqiao powder groups. After repeated cold-warm stimulation for 6 hours, the rats in the negative control group and model group were given distilled water, the Mahuang decoction group was given 2. 43 g crude drug / kg body weight Mahuang decoction, and the Yinqiao powder group was given 16. 74 g crude drug / kg body weight Yinqiao powder once a day for 7 days 30 minutes after the last stimulation. Except for the negative control group, the other groups were re-subjected to repeated cold-warm stimulation, and the medicines were given twice at 6 and 22 hours after stimulation. Nasal lavage fluid was prepared, nasal mucosal tissue was extracted, and blood was obtained for detecting the corresponding indexes at 24 hours. Results After repeated cold-warm cycle stimulation, IgA protein expression in the nasal mucosa was significantly decreased at days 1 and 3 and then gradually increased and returned to normal on day 7. When rats were re-stimulated by cold-warm cycles, IgA protein expression in the nasal mucosa was significantly decreased, and the amounts of lysozyme and PGE2 in nasal lavage fluid were significantly decreased on days 1 and 3. The serum level of TNF-α remained high, and the contents of PGE2 and IL-1β were significantly increased on days 1 and 3. In contrast, the IL-6 content only increased on day 1 after stimulation. Both Mahuang decoction and Yinqiao powder interventions increased IgA protein expression in the nasal mucosa and sIgA content in nasal lavage fluid. Yinqiao powder also increased the amount of lysozyme in nasal lavage fluid and decreased the serum contents of TNF-α and IL-1β. Conclusions Repeated cold- warm stimulation decreases the function of the nasal mucosal immune barrier and increases the release of several types of inflammatory factors in rats. Mahuang decoction and Yinqiao powder improve the function of the nasal mucosal immune barrier. Mahuang decoction increases the IgA content, and Yinqiao powder reduces inflammatory factors to a greater extent.
ZHAO Jianqing , DING Lu , ZENG Junyi , YING Guoqiu , WEN Yuan , NIE Jungang , YI Dasong
2021, 29(6):724-729. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 003
Abstract: Objective To study the chronological changes in myocardial fibrosis in spontaneously hypertensive rats. Methods Forty-five male spontaneously hypertensive rats (SHR) and 35 male Wistar Kyoto rats (WKY) that were four weeks old and specific-pathogen-free were randomly selected and fed in cages until 42 weeks. Systolic blood pressure was measured by the tail-cuff method , and cardiac structure and function were detected by echocardiography at pre-set time points. At the same time points, heart specimens were dissected, and the left ventricular mass index (LVMI) was calculated. Myocardial fibrosis of the left ventricle was detected by Masson staining, and TGF-β1, collagen I and collagen III were detected by qRT-PCR. Results The blood pressure of SHR increased rapidly from 6 weeks to 12 weeks and was significantly higher than that of WKY rats at 12 weeks (P< 0.05) and then stabilized and remained high. With age and blood pressure changes, the structure-related indexes of the left ventricle, including interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT) and LVMI, all showed dynamic characteristic alterations. The collagen volume fraction (CVF) gradually increased with the age of SHR and was significantly higher than that of WKY rats at 12 weeks and later ( P< 0.05). The expression of the fibrosis-related factors TGF-β1, type I collagen and type III collagen in the left ventricle myocardium of SHR all decreased at first and then increased with age to statistically significant levels after 32 weeks. Conclusions With increasing age and blood pressure, myocardial fibrosis in SHR continuously develops and presents with the typical characteristics of chronological changes, including structure, function, macro and micro alterations.
XU Zhiling , ZHANG Bin , ZHANG Shuncai
2021, 29(6):730-737. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 004
Abstract: Objective To investigate the role and mechanism of NOD2 ( nucleotide-binding oligomerization domain 2, NOD2), a pattern recognition receptor in liver cells, in the process of liver inflammation. Methods NOD2 liver-specific knockout mice were used, and diethylnitrosamine (DEN) was used to construct an acute liver injury model. NOD2 knockout mice injected with DEN were used as the Nod2△hep model group, and injected with DEN B6 / JNju- Nod2em1Cflox / Gpt (Nod2f/ f ) mice are Nod2f/ f model group, NOD2 knockout mice without DEN injection are Nod2△hep group, Nod2f/ fmice without DEN injection are Nod2f/ f group. He staining was used to detect the effect of DEN on liver pathological damage, ALT and AST kits were used to detect the changes of serum ALT and AST levels; F4 / 80 immunohistochemical staining was used to detect the number of hepatitis cells and real-time quantitative qPCR was used to detect the gene expression level of inflammatory factors in liver cells; Ki67 immunohistochemical staining and TUNEL staining were used to detect the effects of den on liver cell proliferation and apoptosis Western blot was used to detect the expression of NF-κB, MAPK and STAT3 signaling pathway related proteins Result Compared with Nod2f/ fmodel group, Nod2△hep model group mice liver tissue pathological damage was significantly reduced, manifested as cell necrosis and vacuolization, and Nod2△hepmodel group mice serum ALT and AST levels Significantly decreased (P<0.01). In addition, compared with Nod2f/ f model group, the inflammatory factors TNF-α, IL-6, IFN-γ and IL-1β expression levels、the number of F4 / 80 staining positive cells in liver tissue、the proliferation and apoptosis levels of the hepatocytes in Nod2△hep model group were significantly reduced ( P<0.01); Western blot expression result showed that the P38, ERK, JNK, p65 and JAK2 / STAT3 protein phosphorylation levels in the liver tissue of the Nod2△hep model group were significantly lower than those of the Nod2f/ f model group. However, the Nod2△hep group mice and Nod2f/ fgroup mice used for control had no obvious abnormalities in the above indicators. Conclusions Loss of NOD2 in the liver can significantly inhibit the inflammation and necrosis of hepatocytes in mice, its mechanism maybe related to the down-regulation of expression of NF-κB, MAPK and STAT3 signaling pathways related factors in liver tissue.
CHEN Yuerong , XU Yunyun , NI Wenqin , DING Qike , DAI Wei , XU Yingling , ZHU Xixiao , FANG Jianqiao , WU Yuanyuan
2021, 29(6):738-748. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 005
Abstract: Objective The current study was performed to investigate isobaric tags for relative and absolute quantitation ( iTRAQ)-based quantitative proteomic analysis of the amygdala in rats with complete Freund’ s adjuvant (CFA)-induced chronic pain. A comprehensive analysis of protein expression was performed to explore the underlying mechanism by which electroacupuncture (EA) affects chronic pain. Methods Twenty-seven male Sprague-Dawley ( SD) rats were randomly divided into a control group (control group), model group and EA-treated group (EA group), with 9 rats in each group. Inflammatory pain was induced with an intraplantar injection of 100 μL CFA into the plantar surface of the left hind paw of the male SD rats. EA stimulation of the bilateral Zusanli and Sanyinjiao acupoints was performed for 14 days. Based on iTRAQ-based proteomics analysis, we investigated protein expression in the amygdala. Results EA increased the paw withdrawal thresholds (PWTs) in rats with inflammatory pain induced by noxious stimulation. A total of 6319 proteins were quantified in the amygdala. Of these identified proteins, 58 significantly altered proteins were identified in the model group compared with the con group, and 37 were identified in the EA group compared with the con group. Three proteins were found to be differentially expressed in the amygdala of model rats and EA-treated rats. Conclusions Our study confirms the possible mechanism underlying the effects of EA on the amygdala in rats with chronic pain.
BI Dianyong , WANG Li , HE Zhuqing , YANG Yufang , HE Jiancheng
2021, 29(6):749-757. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 006
Abstract: Objective To study the effect of compound Rehmannia granule on the activation of microglia in the substantia nigra and striatum, the expression of inflammatory factors, and neurobehavior in different rat models. Methods We established a 6-hydroxydopamine (6-ODHA) and a lipopolysaccharide (LPS) animal model by administering a two- point stereotactic injection into the substantia nigra, combined with an intraperitoneal injection of apomorphine. Rats were divided into sham, model (6-ODHA and LPS model groups), and compound Rehmannia granule intervention groups (DH + 6-OHDA and DH + LPS groups). Rats in the drug intervention group were given 7 g / ( kg·d) compound Rehmannia granule suspension by gavage, whereas rats in the sham and model groups were given 2 mL saline by gavage once a day for 6 weeks. Spontaneous rotation behavior induced by apomorphine was observed and recorded after the model was established (abbreviation for 0 weeks) as well as at 2, 4, and 6 weeks after intragastric administration. Tumor necrosis factor-α (TNF- α) and other inflammatory factors in the substantia nigra and striatum were detected using enzyme-linked immunosorbent assay (ELISA). Western Blot was used to detect the expression of ionized calcium-binding adaptor molecule 1 (Iba1) and other proteins in the substantia nigra and striatum. Results (1) For neuroethology, compared with the model groups ( i. e., 6-OHDA and LPS groups), the spontaneous rotation behavior of rats in the compound Rehmannia granule intervention group was significantly lower at 4 and 6 weeks (P< 0.05 and P< 0.001, respectively). (2) The ELISA result showed that compared with the model group, TNF-α and other pro-inflammatory factors in the substantia nigra and striatum of rats in the compound Rehmannia granule intervention group were significantly lower (P< 0.01 and P< 0.001, respectively). (3) Western Blot result showed that compared with the model group, the expression of Iba1 and other pro-inflammatory proteins in the substantia nigra and striatum in the compound Rehmannia granule group were significantly lower (P< 0.05 and P< 0.001, respectively). Conclusions Compound Rehmannia granule intervention inhibits the activation of microglia in the substantia nigra and striatum, downregulates the expression of TNF-α and proinflammatory factors, and attenuates the spontaneous rotation behavior of model rats.
SHEN Xuemei , PENG Xi , YE Qiaobo , YE Zhen , DENG Qin , WANG Juan , WEN Changlin , YUAN Shibin
2021, 29(6):758-767. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 007
Abstract: Objective Mouse models of ulcerative colitis (UC) were established with sodium dextran sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid ( TNBS) to compare the differences in clinical symptoms, pathological lesions and colonic flora. Methods Thirty male C57BL/ 6 mice were randomly divided into a control group, DSS group and TNBS group. The modeling period was 7 days. Clinical symptoms, including body weight and fecal occult blood, were monitored daily. The colon was harvested at the end of modeling for histopathological diagnosis, and 16S rDNA sequencing technology was used to detect the bacterial composition of the colon contents. Results The clinical result showed that DSS induced diarrhea three days after treatment, fecal occult blood was positive, and body weight was decreased on the fifth day. TNBS treatment decreased body weight on the second day, soft and loose stools were observed from the first to the fourth day, and fecal occult blood was positive. At necropsy, the colon weight in both model groups was increased, whereas the colon in the DSS group was significantly shorter. Histopathologically, the ulcer foci in the colon exhibited a damaged histological structure, and the nearby crypts were dilated in the DSS group, whereas residual crypts accompanied by obvious cell proliferation were observed in the ulcer foci of the TNBS group. The characteristics of colon flora disturbances in the two model groups were different. Compared with the control group, the abundances of Tenericutes and Cyanobacteria were not significantly altered in the DSS group but were increased in the TNBS group (P<0.05). The abundance of Acidobacteria was unchanged in the DSS group but significantly decreased in the TNBS group ( P< 0.05 ). The abundance of Actinobacteria and Lactobacillus was significantly decreased in the DSS group but unchanged in the TNBS group (P<0.05). The abundance of Bacteroidetes was significantly increased in the DSS group but decreased in the TNBS group (P<0.05). Conclusions The UC models induced by DSS and TNBS / ethanol showed similar characteristics in clinical symptoms, pathological changes in colon tissue and intestinal microflora structure, but the two models also exhibited distinct characteristics. The result provide a theoretical reference for animal model selection.
TIAN Weilong , QI Wenjing , LIU Xiaoxiao , SI Jinglei , CHEN Kuirong , CHENG Feng , LI Yueyue , LYU Dongling , LIANG Liang , GAO Jiuyu , FENG Lingli , MO Jiayuan , LAN Ganqiu , LIANG Jing
2021, 29(6):768-776. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 008
Abstract: Objective Recent studies have shown that intestinal microorganisms are associated with metabolic diseases, such as type 2 diabetes mellitus (T2DM), and the reported mechanisms are mostly based on rodent models, but rarely reported in pig models, which are closer to human biology. Methods To explore changes in composition and structure of intestinal microorganisms in a mini-pig model of T2DM, the Guangxi Bama mini-pig was provided a high-fat / high-sugar diet to induce T2DM. After successful induction of T2DM, fresh fecal samples were collected from individuals in the T2DM and control (CN group, fed a normal diet) groups, and 16S rRNA gene sequencing technology was used to analyze the composition and structure of intestinal microorganisms. Results The sequencing result showed that the diversity of intestinal microorganisms was decreased in T2DM group versus CN groups. At the phylum level, the abundance of Firmicutes and Bacteroides was significantly increased and decreased, respectively, in T2DM group compared with the CN group. At the genus level, principal coordinates analysis showed that the composition of the CN group was significantly different from that of T2DM group, and the T2DM group had a unique genus of Mitsuokella related to succinic acid production. Comparison of the two groups and linear discriminant analysis effect size analysis showed that several bacteria exhibited significant differences between the two groups, such as Oscillospira, Prevotella and Peptococcus, which were significantly enriched in the CN group, and g__Intestinibacter, which was significantly enriched in the T2DM group. There were no significant differences in metabolic pathways between the two groups. The two groups were mainly enriched in pathways assigned the biosynthesis of amino acids, carbon metabolism, amino sugar and nucleotide sugar metabolism, glycolysis and gluconeogenesis. Conclusions In this study, we found the characteristics of intestinal microorganism variation and the potential microorganisms closely associated with the occurrence of T2DM in mini-pigs. These findings provide a theoretical basis for the study of the association and related mechanisms between intestinal microorganism and T2DM .
HUANG Shuwu , MIN Fangui , WANG Jing , LUO Yinzhu , HE Lifang , CHEN Meiling , PAN Jinchun
2021, 29(6):777-784. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 009
Abstract: Objective To conduct a comparative study of the intestinal flora in six common strains of mice and rats. Methods In this study, 210 feces or intestinal content samples were collected from 150 SPF mice and rats from three experimental animal production units. PCR amplification of the samples was carried out based on common primers of the bacterial 16S rDNA V3-V4 region, and then the Illumina HiSeq 2500 high-throughput system was used for sequencing. Based on the animal source, breed, gender, age and intestinal segmentation ( duodenum, jejunum, ileum, cecum, colon and rectum) factors, bioinformatics method and cluster analysis of differences were applied to analyze the diversity in the structure of the intestinal flora in rats and mice. Results The intestinal flora of experimental mice or rats with the same source had the highest similarity, whereas the intestinal flora of experimental mice and rats showed certain differences due to the type of species. The intestinal flora from different intestinal segments of experimental mice exhibited certain differences, and stool samples were more similar to the colonic intestinal flora. Under the same breeding and living environment conditions, the species, age and intestinal segment of experimental mice and rats are the main endogenous factors that determine the structure of the intestinal flora, and the effect of strain and gender on their intestinal flora is minimal. Conclusions This study revealed the diversity and differences in the intestinal flora of common mice, explored the influencing factors of the host intestinal flora, and provided more basic data for the relationship between intestinal flora and diseases.
MA Qi , WENG Yujing , LI Jia , QIN Shiyuan , HE Yanfeng , MA Xudong
2021, 29(6):785-792. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 010
Abstract: Objective To explore the curative effect of Shenling Baizhu powder on dextran sulfate sodium (DSS)- induced ulcerative colitis (UC) model mice. Methods Thirty-six male BALB/ c mice (6 ~ 8 weeks, 18 ~ 20 g) were randomly divided into 6 groups with 6 mice in each group: group A, high-dose Shenling Baizhu powder; group B, middle- dose Shenling Baizhu powder; group C, low-dose Shenling Baizhu powder; group D, sulfasalazine treatment; group E, blank control; and group F, model. The acute UC model was established by administering 3. 5% dextran sulfate sodium solution with drinking water for 7 days, and at the same time of modeling, different drugs were given by intragastric administration. The therapeutic effect of Shenling Baizhu powder on UC mice was evaluated by assessing their clinical manifestations, disease activity index (DAI), colon and rectum length, colon mucosa injury and colon histopathology. Results Compared with group E, the DAI score was evidently higher, the colon was markedly shorter, and the visual score and histopathology score of colonic mucosa injury were significantly higher in group F. The condition of group B was better than that of groups A, C and D. The score of colonic mucosal injury in group F was distinctly higher than that in group B (P< 0.05). Shenling Baizhu powder improved the local injury of colon tissue and relieved the symptoms of UC. Conclusions Shenling Baizhu powder has a good therapeutic effect on UC model mice, and the curative effect of a middle dose of Shenling Baizhu powder was better than that of the high and low doses of Shenling Baizhu powder.
CHEN Haohao , ZHANG Yanfang , PAN Xiaoming , GAO Suhua , ZHANG Hui , LOU Hongqiang
2021, 29(6):793-799. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 011
Abstract: Objective To establish a method of Campylobacter jejuni colonization in the intestine of C57BL/ 6 mice through antibiotic-induced microbiome depletion. Methods Thirty-six C57BL/ 6 female mice were divided into normal, control and experimental groups. After 2 days of cefoperazone sodium and sulbactam sodium intragastric administration (50 mg / mL), 200 μL of Campylobacter jejuni were administered intragastrically. 16S rDNA analysis was performed to detect intestinal contents on days 1 ~ 3 post modeling. Animal feces were collected, and the HipO gene of Campylobacter jejuni was detected by TaqMan qPCR on days 1 ~ 7 post modeling. Immunofluorescence was used to detect the colonization of Campylobacter jejuni in the intestinal tissues of mice at 1, 2, 3 and 7 days, and the pathological changes were observed by HE staining. Results In the experimental group, the Lactobacillus of the ileum and Bacteroides of the cecum and colon were inhibited. Additionally, the relative abundance of Enterococcus was increased, and a higher abundance of Campylobacter was detected on day 1. Higher Campylobacter jejuni copy numbers were detected in the feces of the experimental group by TaqMan qPCR on days 1~ 3, and immunofluorescence-labeled Campylobacter jejuni were clearly observed in the intestinal lumen. The intestinal mucosa was mainly intact and showed no obvious inflammatory cell infiltration. Conclusions Microbiome depletion induced by cefoperazone sodium and sulbactam sodium promoted the short- term colonization of Campylobacter jejuni in the intestine of mice.
PENG Dongdong , CHEN Xiangchi , XIA Wei , LIU Xuewu , WANG Fei
2021, 29(6):800-807. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 012
Abstract: Objective To establish a susceptible pneumonia model of mixed bacteria, including Staphylococcus aureus, Streptococcus pneumoniae and Escherichia coli, and provide a useful animal model for drug efficacy evaluation. Methods Thirty-six healthy adult SD rats ( 50% male and 50% female) were randomly divided into the blank group, model group and erythromycin group, with twelve rats in each group. After the animals in each group were anesthetized with diethyl ether, the model group and erythromycin group were instilled with 1×108 CFU/ mL mixed bacterial solution (0. 5 mL each rat), and the blank group was instilled with an equal volume of saline. After 2 h, the drug was administered three times for 10 min each time in 4 h intervals, followed by continuous administration for the next 7 days. During administration, the general state of rats in each group was observed. On the 3rd and 7th day of modeling, the lung function of rats was evaluated, and the number of white blood cells and percentage of neutrophils in bronchoalveolar lavage fluid (BALF) were determined. ELISA was used to detect interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in BALF. HE staining was performed to observe the pathological changes and count the bacterial cultures in lung tissues. Results Compared with the blank group, the model group showed significantly increased body temperature, WBC, Neu%, TNF-α and IL-6, significantly decreased FVC, FEV200 / FVC and VT, damaged alveolar structure, a large number of infiltrated inflammatory cells and interstitial lung thickening. Compared with the model group, the erythromycin group exhibited significantly decreased body temperature, WBC, Neu%, TNF-α and IL-6 and significantly increased FVC, FEV200 / FVC and VT. Rat lung histopathological changes were significantly alleviated. The number of Staphylococcus aureus,Streptococcus and Escherichia coli were significantly reduced. Conclusions In this experiment, a mixture of Staphylococcus aureus, Streptococcus pneumoniae and Escherichia coli was instilled into the lungs of rats through the trachea to establish a model of bacterial pneumonia, and this model can be used to evaluate the effect of drugs.
HUA Weicheng , FU Pengyu , ZHANG Ying , WANG Linjia , NI Zhen , GONG Lijing
2021, 29(6):808-815. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 013
Abstract: Objective Lipophagy is a type of selective autophagy that targets fat and is regulated by FoxO1. Exercise is an effective method to regulate lipid metabolism disorders. Whether the regulation of hyperlipidemia is mediated by the FoxO1-lipophagy pathway remains unreported. In this study, two types of exercise were used as interventions in hyperlipidemia model mice, and the changes in lipophagy-related indexes in adipose tissue were detected to explore the possible mechanism by which exercise alleviates hyperlipidemia. Methods C57BL/ 6J mice were selected as the wild-type control group (WT group). The hyperlipidemia model was constructed by apolipoprotein E gene knockout (ApoE- / - ), and mice were divided into three groups: the silent control group (CON group), moderate-intensity continuous training group (MICT group) and high-intensity intermittent training group (HIIT group). After 6 weeks of intervention, the blood lipid levels in each group were detected, and the morphology of adipocytes was observed by HE staining. The changes in PI3K, Akt / p-Akt, FoxO1 / p-FoxO1 and autophagy-related indexes (Beclin1, Atg7, LC3, p62 and Rab7) in adipose tissue were measured by RT-qPCR and Western Blot. Results (1) Plasma TG, TC and LDL-C levels in the CON group were significantly increased compared with the WT group, and TG and TC levels in the exercise groups were significantly decreased compared with the CON group (P< 0.01). (2) HE staining showed that the number of adipocytes in the CON group were increased, compared with the WT group in the same field (P< 0. 01). (3) Compared with the WT group, the mRNA expression levels of FoxO1, Beclin1, Atg7, LC3 and Rab7 were increased in the CON group, and the expression levels of PI3K, p-Akt / Akt, p-FoxO1 / FoxO1 and P62 were decreased (P< 0.01). In addition, Beclin1, Atg7, LC3 and Rab7 protein contents were increased (P< 0.01). The mRNA levels of FoxO1, Beclin1, LC3, Atg7 and Rab7 in the MICT group and HIIT group were lower than those in the CON group, whereas the protein contents of PI3K, p-Akt / Akt, p- FoxO1 / FoxO1 and p62 were increased (P< 0.05 or P< 0.01). The protein contents of Beclin1, Atg7, LC3 and Rab7 were decreased (P< 0.05 or P< 0.01). Conclusions These Results suggest that both MICT and HIIT alleviate hyperlipidemia by inhibiting of the FoxO1-lipophagic signaling pathway in adipocytes, thereby regulating lipid levels.
HE Yun , CHEN Yisheng , REN Lan , YIN Yijie , HU Guiling , WU Yunli
2021, 29(6):816-822. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 014
Abstract: Objective Microcystin contamination caused by cyanobacteria blooms is a profound global concern. Microcystin-LR (MC-LR) was documented to induce potent hepatotoxicity, but the exact mechanisms have not been fully elucidated. To better understand the mechanisms, we conducted the following investigations. Methods Primary mouse hepatocytes were isolated, purified and exposed to a MC-LR concentration range of 2. 5 ~ 10 nmol / L for 48 h with DMEM treatment as the negative control. Mitochondrial function ( ATP levels and mitochondrial membrane potential), DNA damage (comet assay and 8-OHdG levels) and p53 expression were determined in MC-LR-treated cells and control cells. In addition, experiments were repeated to assess mitochondrial function after pft-α preconditioning. Results MC-LR led to a progressive loss in ATP production and mitochondrial membrane potential in a dose-dependent manner. Furthermore, the comprehensive DNA damage examination and upregulated p53 protein level indicated that MC-LR was associated with DNA damage in primary mouse hepatocytes. However, when p53 was blocked by PFT-α, mitochondrial damage was attenuated after MC-LR treatment. Conclusions Together, these data indicate that MCLR-induced DNA damage promoted p53 production, which was associated with mitochondrial dysfunction.
WANG Kai , HOU Yujun , SONG Wei , CHEN Ying , JIANG Huiling , TAN Yu , ZHOU Siyuan
2021, 29(6):823-829. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 015
Abstract:Diarrhea is a common disease in traditional Chinese medicine (TCM), and dialectical treatment with TCM often achieves better result. Establishing animal models of TCM syndromes is of great significance to TCM research. Simple animal model establishment method are conducive to the development of TCM. At present, there is no uniformly recognized standard for establishing TCM syndrome models of diarrhea. The author of this article reviewed the method for generating animal models of diarrhea, including intestinal dampness-heat syndrome, cold-dampness trapping the spleen syndrome, stagnation of spleen and stomach syndrome, liver depression and spleen deficiency syndrome, spleen-qi deficiency syndrome and spleen-kidney yang deficiency syndrome, and found that the current approaches are unclear because of the random selection of modeling factors, subjective model evaluation criteria and other issues. This review provides suggestions for model improvement to establish industry-recognized, simple, efficient, scientific and stable diarrhea TCM syndrome models.
JIANG Ning , ZHANG Yiwen , YAO Caihong , HUANG Hong , LIU Xinmin
2021, 29(6):830-838. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 016
Abstract:Depression is a common mental disease with a high prevalence, disability rate and recurrence rate. The pathobiology of depression is multifactorial and not yet completely understood. Animal models and behavioral tests of depression have become essential for developing antidepressant drugs. The core symptoms of depression in depressive rodent models, including anhedonia and despair behaviors, are evaluated by different types of behavioral tests, such as the sucrose preference test, novelty-suppressed feeding test, tail suspension test, forced swim test and others. In this review, the principles and method of behavioral tests for depression that are currently used for antidepressant discovery are discussed and assessed. Moreover, the commonly used animal models of depression are summarized. This review provides valuable information for selecting the appropriate modeling method and behavioral tests according to the purpose of the study. This review aims to serve as a reference for researchers to select common behavioral tests and animal depression models, which may be of great significance for the in-depth study of depression.
SHEN Ming , CHEN Yanwen , LI Yang , YANG Lingling , LIANG Qiankun , MING Haixia
2021, 29(6):839-847. DOI: 10. 3969 / j.issn.1005-4847. 2021. 06. 017
Abstract:Tumor metastasis is a complicated process. The concept of the pre-metastatic niche (PMN) reveals the essential factors of tumor metastasis. Experimental animal models have made significant contributions to simulating the process of human diseases, developing new drugs and therapies and clinical trials. In particular, they have been widely used in the study of tumor behavior. The pulmonary metastasis tumor models have the advantages of high reproducibility, high success rates and promising experimental result . Based on the concept of PMN, this article summarizes the method and evaluation indicators of pulmonary metastasis animal models.
