基于PI3K-Akt-mTOR及PI3K-Akt-GLUT4信号通路探讨芪苓温肾消囊方治疗多囊卵巢综合征大鼠的作用机制*

作者：周黎阳1，陈 萍2，丁春丽2

单位：1.河南中医药大学第一临床医学院，河南 郑州 450046； 2.河南中医药大学第一附属医院，河南 郑州 450099

引用：引用：周黎阳，陈萍，丁春丽.基于PI3K-Akt-mTOR及PI3K-Akt-GLUT4信号通路探讨芪苓温肾消囊方治疗多囊卵巢综合征大鼠的作用机制[J].中医药导报,2025,31(9):61-67.

DOI：10.13862/j.cn43-1446/r.2025.09.010

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摘要：

目的：基于磷酸肌醇3-激酶（PI3K）-蛋白激酶B（Akt）-哺乳动物雷帕霉素靶蛋白（mTOR）及PI3K-Akt-葡萄糖转运蛋白4（GLUT4）信号通路探讨芪苓温肾消囊方治疗多囊卵巢综合征（PCOS）大鼠的作用机制。方法：从65只雌性SD大鼠中随机选10只作为对照组，正常饲料喂养，剩余55只大鼠以来曲唑联合高脂饲料诱导建立PCOS大鼠模型。将造模成功的大鼠随机分为模型组、二甲双胍组（0.1 g/kg）、芪苓温肾低剂量组（1.8 g/kg）、芪苓温肾中剂量组（3.6 g/kg）、芪苓温肾高剂量组（7.2 g/kg），每组10只。对照组和模型组大鼠予生理盐水灌胃，其余各组给予对应药物，1次/d，连续21 d。记录各组大鼠体质量。HE染色观察卵巢形态学变化；血糖仪检测空腹血糖（FBG）水平；酶联免疫吸附试验（ELISA）法检测血清卵泡刺激素（FSH）、黄体生成素（LH）、雌激素（E2）、总睾酮（T）、甘油三酯（TG）、总胆固醇（TC）、空腹胰岛素（FINS）含量，计算稳态模型评估胰岛素抵抗指数（HOMA-IR）；Real-time PCR法检测卵巢组织PI3K mRNA、Akt mRNA、mTOR mRNA及GLUT4 mRNA表达水平；Western blotting法检测卵巢组织PI3K、Akt、mTOR及GLUT4蛋白表达水平。结果：对照组大鼠卵巢组织结构基本正常；与对照组比较，模型组大鼠卵巢组织呈多囊样改变；与模型组比较，芪苓温肾低剂量组、芪苓温肾中剂量组、芪苓温肾高剂量组及二甲双胍组大鼠卵巢组织多囊样改变均改善。模型组大鼠体质量、TG、TC、T、LH、FBG、FINS及HOMA-IR均高于对照组（P＜0.05），FSH及E2水平均低于对照组（P＜0.05）；芪苓温肾中剂量组、芪苓温肾高剂量组及二甲双胍组大鼠体质量、TG、TC、T、LH、FBG、FINS及HOMA-IR均低于模型组（P＜0.05），FSH及E2水平均高于模型组（P＜0.05）。模型组大鼠卵巢组织PI3K mRNA、Akt mRNA、mTOR mRNA及GLUT4 mRNA相对表达量均低于对照组（P＜0.05）；芪苓温肾中剂量组、芪苓温肾高剂量组及二甲双胍组大鼠卵巢组织PI3K mRNA、Akt mRNA、mTOR mRNA及GLUT4 mRNA相对表达量均高于模型组（P＜0.05）。模型组大鼠卵巢组织PI3K、Akt、mTOR及GLUT4蛋白相对表达量均低于对照组（P＜0.05）；芪苓温肾中剂量组、芪苓温肾高剂量组及二甲双胍组大鼠卵巢组织PI3K、Akt、mTOR及GLUT4蛋白相对表达量均高于模型组（P＜0.05）。结论：芪苓温肾消囊方能改善来曲唑联合高脂饲料诱导的PCOS大鼠糖脂代谢、内分泌及卵巢形态学，抑制胰岛素抵抗，其机制可能与激活PI3K-Akt-mTOR及PI3K-Akt-GLUT4信号通路相关。

关键词：多囊卵巢综合征；芪苓温肾消囊方；PI3K-Akt-mTOR信号通路；PI3K-Akt-GLUT4信号通路；大鼠

Abstract：

Objective: To explore the mechanism of Qiling Wenshen Xiaonang prescription (芪苓温肾消囊方) in treating polycystic ovary syndrome (PCOS) based on the expression of phosphoinositide 3-kinase (PI3K) -protein kinase B (Akt) -mammalian target of rapamycin (mammalian target of rapamycin) rapamycin (mTOR) and PI3K-Akt-glucose transporter type4 (GLUT4) signaling pathway. Methods: Among 65 female SD rats, 10 rats were randomly selected as the control group and fed with normal diet. The remaining 55 rats were used to establish the PCOS model by letrozole combined with high-fat diet. The successful model rats were randomly divided into model group, metformin group (0.1 g/kg), Qiling Wenshen low-dose group (1.8 g/kg), Qiling Wenshen medium-dose group (3.6 g/kg), and Qiling Wenshen high-dose group (7.2 g/kg), with 10 rats in each group. The rats in the control group and the model group were given normal saline by gavage, and the other groups were given corresponding drugs once a day for 21 consecutive days. The body weight of rats in each group was recorded. HE staining was used to observe ovarian morphological changes. Fasting blood glucose (FBG) was measured with a blood glucose meter. The levels of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), total testosterone (T), triglyceride (TG), total cholesterol (TC) and fasting insulin (FINS) were detected by enzyme-linked immunosorbent assay (ELISA), and the insulin resistance index (HOMA-IR) was calculated. Real-time PCR was used to detect the expression of PI3K mRNA, Akt mRNA, mTOR mRNA and GLUT4 mRNA in ovarian tissue. Western blotting was used to detect the expression levels of PI3K, Akt, mTOR and GLUT4 proteins in ovarian tissues. Results: The ovarian tissue structure was basically normal in control group. Compared with the control group, the ovarian tissue of the model group showed polycystic changes. Compared with the model group, the polycystic changes of ovarian tissue were improved in the Qiling Wenshen low-dose group, Qiling Wenshen medium-dose group, Qiling Wenshen high-dose group and metformin group. The model group showed higher body weight, TG, TC, T, LH, FBG, FINS and HOMA-IR than control group (P<0.05), while lower levels of FSH and E2 than control group (P<0.05). Qiling Wenshen medium-dose group, Qiling Wenshen high-dose group and metformin group showed lower body weight, TG, TC, T, LH, FBG, FINS and HOMA-IR than model group (P<0.05), while higher levels of FSH and E2 than model group (P<0.05). The model group showed lower relative expression levels of PI3K mRNA, Akt mRNA, mTOR mRNA and GLUT4 mRNA in ovarian tissue than control group (P<0.05). The Qiling Wenshen medium-dose group, Qiling Wenshen high-dose group and metformin group showed higher relative expression of PI3K mRNA, Akt mRNA, mTOR mRNA and GLUT4 mRNA than model group (P<0.05). The model group showed lower relative expression levels of PI3K, Akt, mTOR and GLUT4 protein in ovarian tissue than control group (P<0.05). The Qiling Wenshen medium-dose group, Qiling Wenshen high-dose group and metformin group showed higher relative expression of PI3K, Akt, mTOR and GLUT4 protein in ovarian tissue than model group (P<0.05). Conclusion: Qiling Wenshen Xiaonang prescription can improve glucose and lipid metabolism, endocrine and ovarian morphology and inhibit insulin resistance in PCOS rats induced by letrozole and high-fat diet, which may be related to the activation of PI3K-Akt-mTOR and PI3K-Akt-GLUT4 signaling pathways.

Key words：polycystic ovary syndrome; Qiling Wenshen Xiaonang prescription; PI3K-Akt-mTOR signaling pathway; PI3K-Akt-GLUT4 signaling pathway; rat

发布时间：2026-01-08

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