鹿茸多肽对顺铂所致卵巢早衰大鼠卵巢功能的保护作用及其机制OA北大核心CSTPCD

AIM:To investigate the effect and mechanism of velvet antler polypeptide(VAP)on premature ovarian failure induced by cisplatin(DDP)in rats.METHODS:Female rats with normal estrous cycle were randomly di-vided into the control,model,and VAP groups,with 10 rats in each group.Premature ovarian failure was induced in the model and VAP groups by intraperitoneal injection of DDP(4 mg·kg-1·d-1)for 20 consecutive days,and the VAP group was treated with VAP(400 mg·kg-1·d-1)for 20 consecutive days.Hematoxylin and eosin(HE)staining was used to ob-serve the morphological manifestations of the ovary,and the number of developing follicles at all levels was counted.En-zyme-linked immunosorbent assay(ELISA)was performed to detect serum estradiol(E2),follicle-stimulating hormone(FSH),and anti-Mullerian hormone(AMH)levels.The levels of glutathione(GSH)and malondialdehyde(MDA)in ovarian tissues were detected by biochemical methods.The level of reactive oxygen species(ROS)in ovarian tissue was detected by the probe labeling method.Prussian blue staining was performed to observe the iron accumulation in ovarian tissue,as well as the ferrous ion(Fe2+)level was detected by Fe2+content analysis kit.Immunohistochemistry and West-ern blot analysis were performed to detect the expressions of solute carrier family 7 member 11(SCL7A11),glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)in the ovarian tissue.The fertility of rats was monitored in each group.RESULTS:Compared with control group,the model group showed ovarian atrophy,iron accumulation(P<0.01),reduced development of follicles at all levels and total follicles(P<0.05),increased atretic follicles(P<0.01),reduced litter size(P<0.01),decreased serum E2 and AMH levels(P<0.01),increased FSH levels(P<0.01),decreased GSH level and SCL7A11 and GPX4 protein expression levels in the ovarian tissue(P<0.01),and increased levels of Fe2+,MDA,and ROS and expression levels of ACSL4(P<0.01).Compared with model group,the VAP group had improvement in these aforementioned changes caused by DDP(P<0.01).CONCLUSION:Treatment with VAP can improve ovarian function,maintain normal follicle development,and improve fertility in cisplatin-induced premature ovarian failure rats,and the mechanism may be related to the inhibition of lipid peroxidation and ferroptosis.