基于SIRT1/Nrf2信号通路探讨健脾补肾法改善卵巢早衰模型大鼠氧化应激的作用机制OA

Objective To investigate the mechanism of invigorating spleen and tonifying kidney therapy in regulating premature ovarian failure(POF)in rats,mediated by the SIRT1/Nrf2 signaling pathway and oxidative stress.Methods Fifty SD rats were randomly divided into a blank control group,a model group,low-dose and high-dose Jianpi Bushen Formula(健脾补肾方,JPBSF)groups,and a posi-tive control group,with 10 rats in each group.The general condition,estrous cycle,and body weight changes of the rats were observed.Ovarian histopathology was examined by HE staining.Serum sex hormone levels of E2,FSH,LH,AMH and oxidative stress indicators of SOD,GSH-Px,MDA were detected by ELISA.The mRNA and protein expressions of SIRT1 and Nrf2 in ovarian tissue were detected by RT-PCR and IHC,respectively.The protein expressions of SIRT1,Nrf2,Bax,Bcl-2,and Caspase3 in ovarian tissue were detected by Western blot(WB).Results Compared with the model group,all treatment groups showed improvements in the general condition,disordered estrous cycle,follicular distribution status,and ovarian histopathology.Except for the lack of statistically significant effects on serum SOD and MDA levels in the low-dose JPBSF group(P>0.05),the other treatment groups significantly improved rat body weight,ovarian index,serum sex hormone levels,oxidative indices and the mRNA and protein expressions of SIRT1 and Nrf2 in ovarian tissue,as well as the expressions of Bcl-2,Bax,and Caspase-3 in ovarian tissue(P<0.05;P<0.01).Conclusion The invigorating spleen and tonifying kidney therapy may ameliorate ovarian function by regulating the SIRT1/Nrf2 signaling pathway to reduce oxidative stress-induced apoptosis of ovarian granulosa cells.