甘草酸二铵联合人类胎盘间充质干细胞对大鼠卵巢早衰的改善作用OA

Objective To investigate the protective effects and underlying mechanisms of diammonium glycyrrhizinate(DG)combined with human placental mesenchymal stem cells(hPMSCs)on premature ovarian failure(POF).Methods Forty female Sprague-Dawley(SD)rats with normal estrous cycles were randomly divided into four groups(n=10 per group):blank control(Control),POF model(POF),hPMSCs treatment(hPMSCs),and DG combined with hPMSCs treatment(DG+hPMSCs).The POF model was established by intraperitoneal injection of cyclophosphamide(CTX)for 7 consecutive days.On days 15 and 22 of modeling,rats in the hPMSCs and DG+hPMSCs groups received 1 mL of hPMSCs suspension via tail vein injection.Additionally,the DG+hPMSCs group was administered DG(150 mg/kg/day)via intraperitoneal injection from day 10 for 21 consecutive days.Serum levels of sex hormones,antioxidant enzymes,and inflammatory cytokines were measured by ELISA.Ovarian histopathology was evaluated using hematoxylin-eosin(HE)staining,while protein expression related to ovarian function and inflammation was assessed by Western blot(WB).Results Following CTX induction,the estrous cycle was disrupted,confirming successful POF modeling.Compared with the POF group,both the hPMSCs and DG+hPMSCs groups exhibited increased serum levels of estradiol(E2)and anti-Müllerian hormone(AMH)(P＜0.05),along with decreased follicle-stimulating hormone(FSH)and luteinizing hormone(LH)(P＜0.05).Antioxidant markers,including superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px),were elevated(P＜0.05),while pro-inflammatory cytokines(IL-1β,IL-6,and TNF-α)were reduced(P＜0.05).Ovarian histopathology showed significant improvement,with upregulated expression of CCAAT/enhancer-binding protein β(C/EBP-β)and extracellular signal-regulated kinase(ERK),and downregulated IL-1β,IL-6,and TNF-α protein levels(P＜0.05).Notably,the therapeutic effects in the DG+hPMSCs group surpassed those in the hPMSCs group.Conclusion diammonium glycyrrhizinate exerts antioxidant and anti-inflammatory effects,synergizing with hPMSCs to ameliorate the ovarian microenvironment and enhance the therapeutic efficacy of hPMSC transplantation in POF.