滋肾育胎丸对多囊卵巢综合征模型大鼠子宫内膜胰岛素抵抗及AMPK/PGC-1α信号通路的影响OA

Objective To investigate the effects of Zishen Yutai Pills on endometrial insulin resistance and the AMP-activated protein kinase(AMPK)/PPARγ coactivator-1α(PGC-1α)signaling pathway in polycystic ovary syndrome(PCOS)model rats.Methods Sixty female SD rats were divided into a normal group,a PCOS group,a low-dose(L-)Zishen Yutai Pills group,a high-dose(H-)Zishen Yutai Pills group,and an H-Zishen Yutai Pills+AMPK inhibitor Compound C(CC)group using the random number table method,with 12 rats in each group.Except for the normal group,the PCOS model was established in the other groups by a high-fat diet combined with letrozole gavage.After successful modeling,the PCOS group was administered equal volumes of distilled water via gavage and tail vein injection.The L-and H-dose Zishen Yutai Pills groups were administered 1.6 and 3.2 g/(kg·d)of Zishen Yutai Pills via gavage,respectively,combined with equal volumes of distilled water by tail vein injection.The H-Zishen Yutai Pills+CC group received 3.2 g/(kg·d)of Zishen Yutai Pills via gavage and 0.2 mg/kg of CC by tail vein injection.The normal group received equal volumes of distilled water via gavage and tail vein injection.All groups were administered once daily for 21 consecutive days.The ovarian and uterine weights were compared among groups.An automatic biochemical analyzer was used to determine serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein(LDL),and high-density lipoprotein(HDL),and fasting blood glucose(FBG)levels.Enzyme-linked immunosorbent assay(ELISA)was employed to measure serum fasting insulin(FINS),follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),and testosterone(Testo)levels.The homeostasis model assessment of insulin resistance(HOMA-IR)index and triglyceride-glucose(TyG)index were calculated.Hematoxylin-eosin(HE)staining was performed to detect the pathological changes of ovarian and uterine tissues.Moreover,Western blot was used to detect the AMPK/PGC-1α signaling pathway protein expression levels in the uterus.Results Compared with the normal group,the PCOS group exhibited decreased ovarian weight,uterine weight,serum HDL,FSH,and E2 levels(P＜0.05),increased serum TC,TG,LDL,FBG,FINS,LH,and Testo levels,as well as HOMA-IR and TyG indices(P＜0.05),reduced numbers of corpora lutea and healthy follicles,increased total number of ovarian cystic follicles,decreased endometrial thickness and gland count,along with downregulated p-AMPK and PGC-1α protein expressions in uterine tissues(P＜0.05).Compared with the PCOS group,the L-and H-Zishen Yutai Pills groups showed increased ovarian weight,uterine weight,serum HDL,FSH,and E2 levels(P＜0.05),decreased serum TC,TG,LDL,FBG,FINS,LH,and Testo levels,as well as HOMA-IR and TyG indices(P＜0.05),increased numbers of corpora lutea and healthy follicles,decreased total number of ovarian cystic follicles,increased endometrial thickness and gland count,along with upregulated p-AMPK and PGC-1α protein expressions in uterine tissues(P＜0.05).Compared with the H-Zishen Yutai Pills group,the H-Zishen Yutai Pills+CC group demonstrated decreased ovarian weight,uterine weight,serum HDL,FSH,and E2 levels(P＜0.05),increased serum TC,TG,LDL,FBG,FINS,LH,and Testo levels,as well as HOMA-IR and TyG indices(P＜0.05),increased total number of ovarian cystic follicles,decreased numbers of corpora lutea and healthy follicles,decreased endometrial thickness and gland count,along with downregulated p-AMPK and PGC-1α protein expressions in uterine tissues(P＜0.05).Conclusion Zishen Yutai Pills improve endometrial insulin resistance in PCOS rats,with potential mechanisms related to activating the AMPK/PGC-1α signaling pathway.