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Objective: To investigate the mechanism of the effect of Daodi Tongguan Decoction on ovarian function in rats with premature ovarian failure. Methods: Forty SD female rats with regular estrous cycle were randomly divided into the blank group, the model group, the positive group (Bujiale 0.099 mg/kg), the Daodigitongguan decoction high-dose group (1.4 g/100 g) and the Daodigitongguan decoction medium-dose group (0.7 g/100 g). The model group, positive group, Daodi Tongguan Decoction high-dose group and Daodi Tongguan decoction medium-dose group were given Tripterygium wilfordii polyglycoside tablets suspension (50 mg/kg) by continuous gavage for 14 days to establish a rat model of premature ovarian failure. After the modeling, each group was given the corresponding intervention agent for 28 consecutive days. After the intervention, serum and ovarian tissue were collected from rats in each group. The morphological structure of rat ovarian tissue was observed after HE staining. Serum AMH level was determined by ELISA. The expressions of Bcl-2, Bax and VEGF in ovarian tissue were detected by IHC. The apoptosis of granulosa cells in ovary was observed by TUNEL. Results: Compared to the normal group, the growth follicles in the model group were reduced and the atretic follicles were increased. Serum AMH level was significantly decreased (P<0.01). The expression of Bax protein in ovarian tissue was increased (P<0.01). The protein expressions of Bcl-2 and VEGF were decreased (P<0.01, P<0.05), and the apoptosis rate of follicular granulosa cells in ovarian tissue was increased (P<0.01). Compared to the molding group, the serum AMH level in the TCM dose groups was increased to varying degrees, and the change of the AMH in high-dose group was the most significant (P<0.05). The expression of Bax protein in ovarian tissue decreased (P<0.05), while the expression of Bcl-2 and VEGF protein increased (P<0.05, P<0.05). The apoptosis rate of follicular granulosa cells in ovarian tissue was decreased in the high dose group (P<0.05). Conclusion: Daodi Tongguan Decoction can improve the histological morphology of ovary and relieve ovarian injury, and its mechanism may be related to improving the sex hormone level of POF model rats, reducing the expression level of Bax protein in ovarian tissue, increasing the expression level of Bcl-2 and VEGF protein in ovarian tissue, and reducing the apoptosis rate of follicular granulosa cells in ovarian tissue. [ABSTRACT FROM AUTHOR]

Background: Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta) and interleukin-6 (IL-6)., Methods: Twenty-two male Chinese Guizhou minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ-induced diabetic group (n = 12) and control group (n = 10). STZ (125 mg/kg) was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet beta cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-alpha level in tissue conditioned medium by Western blot. TNF-alpha, IL-1beta and IL-6 mRNA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction (RT-PCR)., Results: Significant elevation in serum glucose levels was observed one month and six months after STZ induction (P < 0.001) and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet beta cells, while in pancreas of diabetic minipigs islet beta cells almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Western blot demonstrated dramatically increased TNF-alpha level in aotic intima conditioned medium, and significant elevation of TNF-alpha, IL-1beta and IL-6 mRNA levels was revealed by RT-PCR., Conclusions: The present study has established Chinese Guizhou minipig models with STZ-induced diabetes. Inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) significantly elevated in aortic intima of diabetic minipigs.