摘要
Objective:To explore the pharmacological effects and molecular mechanisms of a Jiao'ai decoction(JAD)in treating premature ovarian failure.Specifically,we evaluated the receptor for advanced glycation end(RAGE)products pathway,metabolic disorders,and intestinal flora dysbiosis.Methods:Forty female rats with normal estrous cycles were randomly divided into five groups:control,model,estradiol,low-dose JAD,and high-dose JAD,with 8 rats in each.Except for the control group,the rats in other groups were injected intraperitoneally with cisplatin for 8 days(1.5 mg/kg)to establish a premature ovarian failure model.Starting on the fifth day of cisplatin injections,the estradiol,low-dose JAD,and high-dose JAD groups were administered corresponding drugs for 21 days.Sex hormone levels and pathological changes in the ovaries were measured.Key proteins in the RAGE pathway related to apoptosis,aging,and inflammation,were tested using Western blot.A 16S rRNA analysis of feces and non-targeted metabolism in serum was performed to determine the effects of JAD on intestinal flora and metabolism.Results:Body weight,ovarian index,and the number of follicles at all levels increased in the JAD group.Regarding serum hormones,estradiol,anti-mullerian hormone(AMH)and P levels increased,whereas follicle-stimulating hormone(FSH)and luteinizing hormone(LH)levels decreased in the JAD group.The levels of phosphorylated Akt protein(P-Akt),receptor for advanced glycation end products(RAGE),tumor protein p53(P53),C-reactive protein(CRP),apoptosis regulator BAX(BAX)and Caspase3 were downregulated by JAD,whereas B cell leukemia/lymphoma 2(Bcl-2)and Endothelial nitric oxidase synthase(eNOS)were upregulated.JAD was also found to play an important role in the regulation of metabolic disorders and intestinal ecological imbalances by adjusting species composition and diversity.Conclusion:JAD can protect ovaries by exerting anti-inflammatory and anti-apoptotic effects via inhibition of the RAGE pathway.JAD can also regulate metabolic disorders and maintain the dynamic balance of intestinal flora,thereby contributing to the improvement of the ovarian reserve function.
基金
sponsored by the National Natural Science Foundation of China(81673764)
National Key R&D Program of China(022YFC3502301).
