Effect of salidroside on apoptosis of ovarian granulosa cells in polycystic ovary syndrome rats by regulating the HMGB1/TLR4/NF-κB signaling pathway
Objective To investigate the effect of salidroside(Sal)on apoptosis of ovarian granulosa cells in polycys-tic ovary syndrome(PCOS)rats by regulating the high mobility group box 1/Toll-like receptor 4/nuclear factor κB(HMGB1/TLR4/NF-κB)signaling pathway.Methods Rats were randomly divided into control group,Model group,Sal low-dose(Sal-L)group,Sal high-dose(Sal-H)group,and Sal-H+rHMGB1(recombinant HMGB1)group.ELISA was used to measure serum hormones such as estradiol(E2),testosterone(T),luteinizing hormone(LH),and follicle stimulating hormone(FSH).H-E staining was used to observe the pathological morphology of ovarian tissue.The reagent kits were used to detect the content of malondialdehyde(MDA),the activities of superoxide dismutase(SOD)and catalase(CAT)in ovarian tissue.Granulosa cells were separated from ovarian tissue and CCK-8 was used to detect cell proliferation.Flow cytometry was used to detect apoptosis.Western blot was used to detect the expression of Cleaved caspase-3,Bcl-2 associated X protein(Bax),B-cell lymphoma-2(Bcl-2),HMGB1/TLR4/NF-κB pathway related proteins in ovarian tissue.Results Compared with the control group,the structure of ovarian tissue in the Model group was greatly damaged,the serum E2 and FSH levels,the number of corpus luteum,activities of SOD and CAT in ovarian tissue,proliferation rate of ovarian granulosa cell,and ex-pression level of Bcl-2 protein in ovarian tissue were lower,the serum T,LH,and LH/FSH levels,the number of cystic folli-cles,and the apoptosis rate of ovarian granulosa cells,the content of MDA,the expression levels of Cleaved caspase-3,Bax,HMGB1,TLR4,and p-NF-κB/NF-κB protein in ovarian tissue were higher(P＜0.05).Compared with the Model group,the structure and morphology of ovarian tissue in the Sal-L and Sal-H groups were greatly improved,the serum E2 and FSH levels,the number of corpus luteum,activities of SOD and CAT ovarian tissue,proliferation rate of ovarian granulosa cell,and ex-pression level of Bcl-2 protein ovarian tissue were higher,the serum T,LH,and LH/FSH levels,the number of cystic follicles,and the apoptosis rate of ovarian granulosa cells,the content of MDA,the expression levels of Cleaved caspase-3,Bax,HMGB1,TLR4,and p-NF-κB/NF-κB protein in ovarian tissue were lower(P＜0.05).rHMGB1 was able to weaken the im-provement effect of Sal on PCOS rats(P＜0.05).Conclusion Sal can improve sex hormone balance and ovarian tissue damage in PCOS rats,reduce oxidative stress and apoptosis of ovarian granulosa cells,promote the proliferation of ovarian granulosa cells,which may be achieved by inhibiting the HMGB1/TLR4/NF-κB signaling pathway.
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