Effects of Shouwu Wan on Ferroptosis of Premature Ovarian Failure Rats Based on Nrf2/SLC7A11/GPX4 Signal Pathway
Objective To investigate the possible mechanisms of Shouwu Wan on effects of ferroptosis inhibitory protein 1(FSP1),ferritin(Ferritin),nuclear factor E2 related factor 2(Nrf2),solute carrier family7A11(SLC7A11),glutathione peroxidase 4(GPX4)and mitochondrial ferritin(MtFt)in premature ovarian failure(POF)rats.Methods Sixty mature SD female rats were randomly divided into blank group,model group,Shouwu Wan-4 weeks group,Shouwu Wan-6 weeks group,Shouwu Wan prevention group,and Progynova group.Except for the rats in blank group,POF rats model were established in other groups by the intraperitoneal injection of VCD(160 mg·kg-1)for 15 days consecutively.After intragastric administration of Shouwu Wan,the serum sex hormone levels of rats were measured by ELISA;Ultrastructural changes of ovarian granulosa cells(GCs)were observed by electron microscopy.The content of active iron and malondialdehyde(MDA)were detected;Real time fluorescence quantitative PCR and Western blot were used to detect mRNA and protein expression levels of the related factors.Results Compared with blank group,the serum sex hormone levels in model group rats were severely disturbed,and the ultrastructure of ovarian granulosa cells(GCs)was impaired.The number of mitochondria were decreased,and the structure of mitochondrial were abnormal,and vacuolization and autophagosomes could be observed.The concentration of MDA and active iron in rat ovarian tissue significantly increased(P<0.01);The mRNA expression of Ferritin,SLC7A11,GPX4,and FSP1 were significantly decreased(P<0.01),and the protein expression of Nrf2,SLC7A11,GPX4,and FSP1 were significantly decreased(P<0.01).The mRNA and protein expression of MtFt were significantly increased(P<0.01).Compared with the model group,the above changes were significantly improved in each Shouwu Wan intervention group,and the effect of Shouwu Wan prevention group were more significant.Conclusion The mechanism of Shouwu Wan in preventing and treating POF may be related to regulate Nrf2/SLC7A11/GPX4 signal pathway and the expression of FSP1 and MtFt to inhibit ferroptosis.
Shouwu WanPremature ovarian failureRatsFerroptosisNrf2/SLC7A11/GPX4 signal pathway
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