Abstract:Objective To study the role and molecular mechanism of perilla seed oil extract (PSO) in reducing arterial plaque formation and providing cardioprotection in ApoE ^{-/ -} mice. Methods Three-month-old ApoE ^{-/ -} mice were randomly divided into ApoE ^{-/ -}(no drug treatment), low-dose PSO, high-dose PSO and atorvastatin groups. B6 mice of the same age were used as controls (WT group); they were fed a regular diet. After 8 weeks of treatment, biochemical tests, H&E staining, echocardiography, qPCR, ATP detection and Pro-Q Diamond staining were performed. Results Compared with the WT group, ApoE ^{-/ -} mice showed abnormal cardiac structure and function. After PSO treatment, the plaque area was reduced, and cardiac structure and function improved. mRNA expression of ANP, BNP and β-MHC was downregulated, mRNA expression of PPARα and PGC-1α was up-regulated, and the intracellular content of ATP and the phosphorylation level of TnI were increased. Conclusions PSO inhibits arterial plaque formation and maintains normal cardiac structure and function in ApoE ^{-/ -} mice. It may regulate the PPARα/ PCG-1α/ NRF-1 axis to increase ATP and myofilament phosphorylation, improve energy metabolism, and exert cardioprotective action.

Abstract:Objective To develop a murine model of age-related macular degeneration (AMD), using combined chronic exposure to light and hydroquinone, and to characterize the pathological and ultrastructural changes, and retinal function, thus to provide a more suitable model for AMD pathogenesis and treatment research. Methods Twenty 4-monthold C57BL/6 mice were randomly divided into a model group and a normal group, with 10 mice in each. The mice in the model group were fed a diet containing 8 g/ (kg·bw) hydroquinone and received 12 h light exposure daily with an intensity of 2500 lx. Mice in the normal group were fed with the same diet without hydroquinone, and were exposed to conventional illumination. After 3. 5 months, light and electron microscopy and electroretinograms (ERGs) were used to detect structural and functional changes in the retina. Photoreceptor apoptosis was evaluated with TdT-mediated dUTP nick-end labeling (TUNEL) staining, and vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) expression and distribution were detected by immunofluorescence. Results ERGs showed that retinal function of the mice in the model group was lower than that of mice in the normal group. Light microscopy showed atrophic changes in the retinal pigment epithelium (RPE) layer in the model group, and a reduced number of photoreceptor cells (164. 67±34. 37 versus 243. 33±15. 23 in the normal group). There were significantly fewer photoreceptor cells in the model group than in the normal group (t =-9. 77, P <0. 05). Transmission electron microscopy showed that the photoreceptor outer segments of the mice in the model group were loose, deformed and partially fragmented. In addition, the RPE-cell microvilli were shortened; the Bruch’ s membrane became irregularly thickened; and endothelial cells from the choroidal capillary basement membrane penetrated into the Bruch’ s membrane. Apoptosis was rarely found in the normal group. TUNEL staining showed that there were many positive cells in the RPE and photoreceptor layers in the model group. The apoptosis rate was (43±2. 73)% ( P <0. 01). Immunofluorescence showed marked VEGF-positive staining in the RPE layer in the model group, whereas no specific staining was found in the normal group. Immunofluorescence of CD31 showed scattered positive staining in the outer plexiform layer and ganglion cell layer in the normal group, whereas it could also be found in the RPE layer in the model group, which indicated the development of neovascularization. Conclusions The retinas of mice treated with combined hydroquinone and chronic light damage closely mimic the development and characteristics of human AMD, this may provide a reliable animal model for further studies of AMD pathogenesis and management.

Abstract:Objective The ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass/ mass spectrometry (UPLC-Q/ TOF-MS/ MS) urine metabolomics method was used to screen for potential metabolic markers of rat model of damp-heat diarrhea and to explore the pathogenesis. Methods The rat model of damp-heat diarrhea was established using a high-sugar and high-fat diet (HF), a high-temperature and high-humidity environment (HH), and intraperitoneal injection of Escherichia coli (EC). Urine samples were collected from rats at different stages of modeling (HF, HH, and EC) and analyzed using UPLC-Q/ TOF-MS/ MS. The data were analyzed by multivariate statistical analysis. Results Seven potential endogenous biomarkers were screened, namely, L-glutamic acid-L-cysteine, L-formyl kynurenine, 5-hydroxy-N-formylkynurenine, riboflavin-5-phosphate, linoleic acid, L-tryptophan and melatonin. Conclusions The metabolic pathways involved in damp heat diarrhea include metabolic pathways such as tryptophan metabolism, riboflavin metabolism, and linoleic acid metabolism. The results suggest that energy-, amino acid- and lipidmetabolism disorders occur in rats with damp-heat diarrhea which provide a scientific basis for elucidating the mechanism of pathogenesis of Chinese medicine and traditional Chinese veterinary medicine damp-heat diarrhea.

Abstract:Objective To investigate the immunoregulatory effect of P38 mitogen activated protease ( p38 MAPK) signals in rats with diarrhea-predominant irritable bowel syndrome (D-IBS). Methods Forty SPF Wistar rats (half male and half female) were randomly divided into a control group, and D-IBS model I (7 d), II (14 d) and III (21 d) groups, with 10 rats in each group. Rats in the model groups were developed through chronic restraint and senna decoction gavage, whereas the control rats were gavaged with the same volume of pure water. The D-IBS rates were killed on the seventh, fourteenth and twenty-first days, respectively. Rats in the control group were killed on the twenty-first day. The serum levels of IL-1β, IL-6 and TNF-α were measured by ELISA. The pathological changes in colon tissue were observed with hematoxylin and eosin (H&E) staining, and the p38 MAPK protein expression in the colon tissue was assessed with immunohistochemistry. Results Compared with the control group, the IL-1β, IL-6 and TNF-α levels in serum, and the p38 MAPK protein expression in colon tissue of the model groups were significantly higher ( P <0. 05, P <0. 01). The expression of p38 MAPK was positively correlated with IL-1β, IL-6 and TNF-α. Conclusions The D-IBS rat model, developed through chronic restraint and senna decoction gavage, may have upregulation of the expression of p38 MAPK, promoting the release of IL-1β, IL-6 and TNF-α, and inducing mild inflammation of the intestinal mucosa by activating the p38 MAPK signal pathway.

Abstract:Objective To establish and evaluate a mouse model of human flora-associated (HFA)from patients of coronary heart disease via fecal microbiota transplantation. Methods Twenty-eight female germ-free (GF) C57BL/6J mice were divided into the healthy control (CON) and coronary heart disease (CAD) groups. Eight-week-old mice were orally inoculated with 0. 4 mL of stool suspension from healthy participants or CAD patients to build the HFA mouse model. At 6 and 10 weeks post-inoculation, fresh fecal samples were collected and examined for the V3 region of the 16S rDNA gene. Blood sera were collected and examined for blood lipid, cholesterol, myocardial enzymes and cytokine levels. Coronary arteries were collected, processed and stained with hematoxylin and eosin (H&E) for pathological examination. Results The average body weight of the CAD group was significantly higher than that of the CON group ( P <0. 05) from 5 weeks post-inoculation. α-diversity analysis showed that the Simpson ( P <0. 05, P <0. 01), Chao1 ( P <0. 05) and ACE indices ( P <0. 05) were significantly lower in the CAD group than that in the CON group. The Shannon index ( P <0. 05, P <0. 01) was higher in the CAD group than in the CON group at 6 and 10 weeks post-inoculation. The intestinal florae were mainly comprised of the phyla Firmicutes, Proteobacteria, Bacteroidetes, Verrucomicrobia, Fusobacteria, Actinobacteria, Cyanobacteria and Tenericutes. At six weeks post-inoculation, the relative abundances of Firmicutes and Tenericutes were lower ( P <0. 05), and those of Bacteroidetes and Verrucomicrobia were higher ( P <0. 01) in the CAD group than in the CON group. At ten weeks post-inoculation, the relative abundance of Firmicutes ( P <0. 01) was lower, and the relative abundances of Bacteroidetes and Verrucomicrobia ( P <0. 01) were higher in the CAD group than in the CON group. β- diversity analysis showed that the CON and CAD groups were distributed in different quadrants, but the same groups at different stages were distributed in the same quadrants, with a significant difference between the groups ( P <0. 05). The serum levels of TG ( P <0. 05, P <0. 01), TC ( P <0. 05), LDH ( P <0. 01, P <0. 0001) and CK ( P <0. 01, P <0. 05) were significantly higher in the CAD group than in the CON group at 6 and 10 weeks post-inoculation. LDL-C levels were significantly higher ( P <0. 05) in the CAD group than in the CON group at 10 weeks post-inoculation. IL-6 levels were higher at 6 weeks ( P <0. 05) and lower at 10 weeks ( P <0. 01) post-inoculation in the CAD group than in the CON group. The IL-2, IL-4, IL-5 and IL-1β levels were significantly higher ( P < 0. 0001, P < 0. 05, P < 0. 0001, P < 0. 01, respectively) in the CAD group than in the CON group at 10 weeks post-inoculation. IL-12p70, TNF-α and INF-γ levels did not differ between the CAD and CON groups. Pathological examination using HE staining of the coronary arteries showed no obvious atherosclerotic changes (e.g., foam cell infiltration). Conclusions A mouse model of HFA from CAD patients was established via fecal microbiota transplantation. The main advantages of using bacteria from CAD patients are that the GF mice were well colonized, and the animals have similar body weights and serum levels of blood lipid, cholesterol and cytokines.

Abstract:Objective To evaluate the differences between three commonly used methods for establishing mouse models of premature ovarian insufficiency (POI), and to determine the method that is most accordant with the clinical features of POI. Methods Ninety-six ICR mice with regular estrous cycles were randomly divided into 4 groups: the control group (A), the tripterygium glycosides (TG) group (B), the 4-vinylcyclohexene diepoxide (VCD) group (C), and the D-(+)-galactose (D-gal) group (D). After intervention with the different chemicals, eight mice in each group were sacrificed, the serum sex hormone levels were measured, and the pathological changes of uterus and ovaries were examined. Results The level of E2 and the number of follicles differed significantly between mice in the model groups and those in the control group ( P <0. 01). And the estrous cycles in mice of the model groups were significantly irregular whereas those of the control group were regular. Conclusions Mouse models of POI can be successfully established with VCD via intraperitoneal injection. This method has the advantages of being an easier operation and having a higher success rate, as compared with the other two models method. It is the ideal one of the three establishing method and is suitable for popular use.

Abstract:Objective Using infrared thermography to evaluate the rise and fall of Yang in mice with a glucocorticoid drug-induced syndrome. Methods One hundred and twenty SPF male ICR mice were tested in three experiments: each experiment included a normal control group and four groups of different doses of glucocorticoid (hydrocortisone, prednisolone, or dexamethasone), 8 mice in each group. Infrared thermal images of the mice in each group were taken on the fourteenth day of drug administration, and the temperatures at the head, the lateral abdomen and the tail root were analyzed. Results After administration of hydrocortisone and dexamethasone, all the maximum head temperature, the mean trunk temperature and the minimum tail temperature of the mice were decreased to different degrees. After prednisolone administration, the maximum head temperature of mice in the very-low-dose glucocorticoid group showed a significant decrease. Conclusions Infrared thermography can be used to evaluate the degree of “Yang” in experimental mice. Hydrocortizone and dexamethasone can induce cold signs similar to Yang deficiency in mice with drug-induced deficiency syndromes.

Abstract:Objective This study was designed to evaluate the effect of short-term exposure to the particulate matter with diameters that are generally 2. 5 μm and smaller (PM_{2. 5} ) on the rat uterine injury, and to determine its mechanism. Methods Thirty Sprague-Dawley rats were randomly divided into: a control group, a 1. 5 mg/ kg body-weight (bw) low-dose PM_{2. 5} exposure group and a 6 mg/ (kg·bw) high-dose PM_{2. 5} exposure group, all of which were followed for 30 days. The pathological uterine changes were observed with hematoxylin-eosin staining (HE staining). Uterine apoptosis was evaluated with the TUNEL method, and the expression levels of cleaved caspase-3 were measured. In addition, the mRNA expression levels of glucose-regulated protein 78 (GRP78), PER-like ER kinase (PERK), eukaryotic initiation factor 2α (eIF2α) and C/ EBP homologous protein (CHOP) were measured with quantitative real-time PCR, and the protein levels involved in the PERK-eIF2α-CHOP signal pathway were tested using western blot assay. Results After short-term exposure, PM_{2. 5} resulted in atrophy and vacuolization of endometrial epithelial cells and glands. The apoptosis rates were (9. 93±1. 66)%, (29. 40±6. 96)% and (43. 58±8. 23)% in the uteruses in the control, low-dose exposure and high-dose exposure groups, respectively. Furthermore, the apoptosis rate was significantly higher ( P <0. 05) in the two exposure groups than in the control group. At the same time, the cleaved caspase-3 protein expression levels in the two exposure groups were significantly increased ( P <0. 05). The results of qPCR and western blot showed that the mRNA and protein levels of GRP78, PERK, eIF2α and CHOP in the two exposure groups were significantly higher than those in the control group ( P <0. 05). Conclusions After short-term exposure to PM_{2. 5}, the uterine structure of the rats is damaged, possibly as a consequence of PM_{2. 5} inducing uterine cell apoptosis via ERs, mediated by the PERK- eIF2α-CHOP pathway.

Abstract:Objective To establish a rat model of hyperuricemia, and explore the possible secondary cardiovascular disease that could be induced by hyperuricemia in the model rats. Methods 32 male SD rats were randomly divided into control group (Group C), potassium oxonate model group (Group M1), potassium oxonate combined with high-sugar model group (Group M2), potassium oxonate combined with yeast extract feed model group (Group M3), 8 rats were treated in each group for 3 weeks. At the end of the experiment, the serum levels of uric acid (UA), blood urea nitrogen, creatinine, insulin (INS), blood glucose (GLU) and triglyceride (TG) were measured, and histopathological examination of liver, renal, and heart tissue was performed. Results Compared with the control group, a significant increase in serum levels of UA ( P <0. 01) and the number of rats showing renal lesions was found in the experimental group (3/8, 37. 5%) after oral administration of potassium oxonate at a dose of 750 mg/ kg, combined with yeast extract feed (Group M3). Also, the changes in GLU, INS, TG and the histopathology of heart tissue (3/8, 37. 5%) suggesting that rats in this group had secondary cardiovascular alterations. Conclusions Compared with the basic potassium oxonate model, the model of potassium oxonate combined with yeast extract feed is more suitable for the study of rat chronic hyperuricemia, accompanied by glucose metabolic impairment. It can also be used in rat models to establish mutual intervention mechanisms between hyperuricemia and cardiovascular disorders, and be applied in comprehensive preclinical pharmacodynamic evaluation of therapeutic drugs for hyperuricemia.

Abstract:Objective To explore the method for detecting intracavernosal pressure ( ICP) under electrostimulation of the cavernous nerve, and to compare the difference between two catheter materials (PE-50 tube needle and intravenous infusion needle) for measurent of ICP. Methods Thirty-six male Sprague-Dawley rats were randomly selected: 16 were randomly selected as the control group, and the remaining 20 were used as the experimental group. Intraperitoneal injections of streptozotocin (60 mg/ kg) were given. After 8 weeks, 16 mice of type 1 diabetes were screened. The control and diabetic groups were further divided into two subgroups, with eight rats in each subgroup. ICP was evaluated using PE- 50 tube needles and other eight rats with intravenous infusion needles. Masson trichrome staining and apomorphine experiment confirmed that the diabetic erectile dysfunction (ED) rat model was successfully developed. After confirming the successful establishment of the model, the ICP tests of the penis were performed, and the erectile function data recorded using the PE-50 tube needle and the intravenous infusion needle were compared. Results Masson trichrome staining showed that the diabetic model group had a smaller area of corpus cavernosum smooth muscle, increased collagen area, and decreased ratio of corpus cavernosum smooth muscle area/ collagen area, all of which were statistically significant ( P < 0. 05). The number of erections in the diabetic model group was significantly lower than that in the control group ( P < 0. 01). Maximum ICP, ICP/ mean arterial pressure, and the area under the curve recorded in the normal and diabetic groups using PE-50 tube needles and intravenous infusion needles were not statistically significantly different ( P > 0. 05), but the slopes were significantly different ( P < 0. 05 or P < 0. 01). Conclusion Both the PE-50 tube needle and intravenous infusion needle can be used in the measurement of ICP during electrostimulation of the cavernous nerve.

Abstract:Objective This experiment is aimed to analyze the expression state of the thyrotropin releasing hormone ( TRH ) gene at different periods in the development of Gymnocypris przewalskii (“Przewalskii′s naked carp”) embryos. Methods The total RNA of G. przewalskii was extracted to make digoxin-labelled antisense mRNA of the TRH gene. In situ hybridization technology and stereomicroscopy were used to observe the expression status of the TRH gene in the G. przewalskii embryos. Results Microscopy showed that positive hybridization signals of the TRH gene appeared in the diencephalon in the 6-8-day embryo, and appeared in the diencephalon, midbrain, hindbrain and medulla in the 9-11-day embryo. The expression level in the diencephalon was higher than that in other brain areas. Conclusions In situ hybridization shows that the THR gene is expressed in 6-11-day embryos of G. przewalskii, suggesting that THR may play an important role in the brain development and maturation in G. przewalskii.

Abstract:Objective To lay a foundation for the study of Meridian gerbils and provide data support for researchers who develop animal models using Meriones meridianus. Methods The morphological indexes, nephron densities and histological characteristics of the kidneys of wild M. meridianus and laboratory Sprague Dawley (SD) rats were compared. Results Comparison of the wild M. meridianus and laboratory SD rats showed that the ratios of medullary to cortical area, inner medullary to cortical area and inner medullary to renal section area were significantly different. In addition, the ratio of proximal and distal tubules per unit area, the kidney/ body weight ratio and nephron density also showed significant interspecies differences. Conclusions The renal morphology and histological characteristics of wild M. meridianus show a significant correlation with their ability to concentrate urine, and are consistent with the characteristics of the kidneys of other drought-tolerant mammals.

Abstract:Objective To construct and identify macrophage-conditional Atg 5-knockout mice to provide an animal model for studying the role of macrophage autophagy in the pathogenesis of renal diseases. Methods LysM-Cre mice were hybridized with Atg 5^{flox/ +} mice, and Atg 5^{flox/ +} mice were self-crossbred to obtain progeny mice with Atg 5^{flox/ +} Cre ^{+/ -} and Atg 5flox/ flox Cre ^{-/ -} . The progeny mice of the above two genotypes were then hybridized to obtain macrophage-conditional Atg 5 gene-knockout mice ( Atg 5flox/ flox Cre ^{+/ -} , Atg 5 ^{-/ -} ) and control mice ( Atg 5flox/ flox Cre ^{-/ -} , Atg 5+/ + ). The phenotypes of the mice were determined via electrophoresis of DNA that had been extracted from mouse tail tissue and amplified via PCR. Mouse bone marrow-derived macrophage RNA and protein were extracted, and Atg 5 gene expression was tested via sequencing and Western blotting. Results A macrophage-conditional Atg 5-knockout mouse model was established; these mice survived and were fertile. The macrophage Atg 5 gene was successfully knocked out at both the gene and protein levels. The basic macrophage autophagy level in the Atg 5 ^{-/ -} mice was much lower than that in the Atg 5+/ + mice (p62 was significantly increased, and LC3II was significantly reduced) and could not be restored to the basic level without deleting Atg 5 after stimulation with the autophagy activator rapamycin. Conclusions Macrophage-conditional Atg 5 - knockout mice are successfully constructed and identified via the Cre / loxp system, providing a research platform for studying the role of macrophage autophagy in renal disease pathogenesis at the animal level.

Abstract:Objective To establish a rat model of pre-eclampsia. Methods Thirty-nine specific pathogen-free pregnant Wistar rats were divided into 3 groups, with 16 in the reduced-uterine perfusion pressure (RUPP) group, 10 in the RUPP+H2O group and 13 in the sham-operation group. RUPP or sham surgery were performed on the 14th gestational day (G14). Blood pressure, urine protein and fetal status were measured on G18. Results (1)Compared with the shamoperation group, the systolic blood pressure, diastolic blood pressure and mean arterial pressure in the RUPP and RUPP+ H2O groups were increased to different degrees in the pregnant rats, but the blood pressure in the RUPP group was unstable. The diastolic blood pressure did not significantly differ between the RUPP and sham-operation groups. The blood pressure of the RUPP+H2O group increased steadily and was significantly higher than that of the RUPP group. The 24-hour urine protein levels were significantly higher in the RUPP group than in the sham-operation group on G18.(2) RUPP surgery significantly reduced the live birth and formation rates on G20. The RUPP operation significantly reduced the fetal weight and placental wet weight compared with those of the sham-operation group, and these effects were the strongest in the RUPP+H2O group. Conclusions The RUPP+H2O method induces a stable clinical manifestation of pre-eclampsia in rats and is recommended as a modified method for modeling RUPP.

Abstract:Objective To investigate the effects of Tianma Xiongling Zhixuan tablets (TXZT) on the blood pressure of spontaneously hypertensive rats (SHRs) and renal hypertensive rats (RHRs). Methods Both SHRs and RHRs were used in the experiment, and the blood pressures of rats in each group were monitored. The left ventricular index (LVMI) of rats in each group was compared by the weighing method, the serum biochemical indexes were detected by ELISA, and the pathological changes of the heart, kidney, brain and aorta were observed using H&E staining. Results The high and middle doses of TXZT significantly lowered the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of RHRs and SHRs rats ( P < 0. 01 or 0. 05), whereas the low dose TXZT significantly lowered the SBP and DBP of SHRs rats ( P < 0. 01 or 0. 05), but had no significant effect on RHRs rats ( P >0. 05). Compared with the untreated model group, the LVMI of SHRs rats treated with TXZT was significantly decreased in the high-dose group ( P <0. 05), but not in other groups ( P >0. 05). Compared with the RHR model group, the values of creatine kinase (CK), creatinine (CREA) and serum urea nitrogen (BUN) values in the high dose TXZT-treated rats were significantly decreased; Lactate dehydrogenase(LDH), CK, CREA and BUN values were significantly decreased with the middle dose group, and BUN values were significantly decreased with the low dose ( P < 0. 01 or 0. 05). Compared with the SHR model group, the CK, CK, CREA and BUN values were decreased, but the difference was not statistically significant ( P >0. 05). Conclusions TXZT has good antihypertensive pharmacological effect on the two different rat models of hypertension, can keep the pulse pressure difference in a certain range, and has a sustaining and stable pharmacological action in regulating blood pressure. TXZT has good preventive and therapeutic effects on hypertension.

Abstract:Objective To investigate the different patterns of cochlear hair cell loss in CBA/ CaJ and C57BL/6J mice with aging. Methods Thirty-two CBA/ CaJ or C57BL/6J mice at 6, 12, 18, and 24 months of age were selected, with 8 mice in each age group. The cochleae were removed under general anesthesia, and then the intact basement membrane was taken out from the cochlea and used for making glass slides of whole cochlear basement membrane. The numbers of cochlear inner and outer hair cells were counted, and input into the computer using cochleogram software. The density of cochlear hair cells in the two mouse strains were compared at corresponding ages, and statistically analyzed. Results The outer hair cells from cochlear apex in the CBA/ CaJ mice at 12 months of age began to loss slightly. With the increase of age, the losses of outer hair cells were continuously expanded, and their developments were mainly from the top to the middle part. The losses of inner hair cells also occurred in the later period. From 18 months of age on, the losses of the cochlear outer hair cells were increased significantly by comparison with that of the last age ( P < 0. 05). However, the losses of the outer and inner hair cells at the cochlear bottom appeared in C57BL/6J mice at the 6 months of age, and the losses were mainly of the outer hair cells. From then on, the losses of outer hair cells were continuously expanded with the increase of age. From 6 months of age on, the losses of the cochlear outer and inner hair cells were increased significantly compared with that of the CBA/ CaJ mice at the same age ( P < 0. 05). From 12 months of age on, the losses of the cochlear outer and inner hair cells were increased significantly compared with that of the same strain( P <0. 05). Conclusions The damages of cochlear hair cells in the CBA/ CaJ mice obey the rule of pathological changes that began at both ends of the cochlear top and bottom, and extended to the middle part, but the damages of hair cells at cochlear top were more serious than that at the cochlear bottom. The damages of cochlear hair cells in the C57BL/6J mice obey the rule of pathological changes that began mainly at the cochlear bottom and gradually extended to the middle and top. The damages of outer hair cells are earlier than that of inner hair cells. The damages of hair cells in C57BL/6J mice are earlier than that in CBA/ CaJ mice. These result suggest that both species of mice can be used as animal models for the research of age-related hair cell apoptosis, but the model of C57BL/6J mouse is more suitable for the research of short-term observation. The differences of hair cell changes between the CBA/ CaJ and the C57BL/6J mice may be related to the mutation and deletion of Cdh23 gene.

Abstract:Owing to the widespread use of glucocorticoids, the incidence of steroid-induced avascular necrosis of the femoral head has increased year by year, but its pathogenesis and possible preventive measures are still unclear. To carry out in-depth research into its fundamental treatment, the establishment of an animal model of steroid-induced avascular necrosis of the femoral head will be the key to success. This paper reviews the research progress of modeling schemes, modeling animals and modeling standards.

Abstract:Animal models can simulate the pathogenesis, pathological changes and clinical symptoms of vascular dementia seen in humans, and provide new ideas for the prevention, diagnosis and treatment of vascular dementia,therefore, important for research of vascular dementia. This paper reviews the rat modeling method for vascular dementia,and provides references for researchers regarding selection of animal models.

Abstract:Stem cells are known as the “ universal cells” in medicine. With the development of medical technology, the method for treating diseases are constantly being updated. Based on the advantages of adipose mesenchymal stem cells (i.e., they are easy to obtain, easy to amplify in vitro, and cause less ethical controversy), an increasing number of researchers focus on this type of stem cells. Therefore, the application of adipose-derived mesenchymal stem cells in animal models is more and more. This article introduces the clinical application of a typical mouse disease model, analyzes the therapeutic effect of adipose-derived mesenchymal stem cells on the disease, and concludes that adiposederived mesenchymal stem cells can differentiate in many ways by secreting cytokines. Based on clinical research and the application of adipose mesenchymal stem cells, immunomodulation may play a role in the treatment of many kinds of diseases.

Abstract:Nickel is a metal that humans are often exposed to during production and daily life. It is an essential trace element in the human body, but in excess, it can harm the body. The exact mechanism of damage caused by excessive nickel exposure remains unclear, but is related to complex cellular and molecular mechanisms. The model of nickel-induced damages forms the basis for studying the mechanisms treatment of nickel-induced damages. The preparation characteristics of different models of nickel poisoning damage are similar, thus, experimental models should be selected according to the experimental purpose. This paper reviews several commonly used methods of modeling nickel poisoning.

Abstract:Thyroid carcinoma ranks first among the malignant endocrine tumors. Immunodeficient mice or rat models of thyroid cancer-cell-line transplantation represent microcosms of human thyroid cancer, which are of great significance for the study of the pathogenesis of thyroid cancer, drug therapy and the mechanism of iodine-131 treatment. Understanding the key influences in the modeling of thyroid cancer immunodeficient mice or rats could improve the success rate of modeling. Therefore, the factors affecting the successful modeling of human thyroid cancer cell-lines in immunodeficient mice and rats are briefly reviewed in this paper.