Zhang Cong-Hui, Xiang Hai-Xin, Wang Xiu-Wen, Xiao He, Wei Fang-Jiao, Yao Jing-Chun, Wang En-Li
School of Pharmacy, Shandong University of Traditional Chinese Medicine Ji'nan 250355, China.
State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Lunan Pharmaceutical Group Co., Ltd. Linyi 273400, China.
Zhongguo Zhong Yao Za Zhi. 2025 Jun;50(12):3368-3376. doi: 10.19540/j.cnki.cjcmm.20250304.401.
Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
采用代谢组学和蛋白质组学方法研究玉脂止血颗粒治疗多囊卵巢综合征伴胰岛素抵抗（PCOS-IR）的作用机制。通过高脂饮食喂养和灌胃来曲唑溶液建立疾病模型，然后用不同剂量的玉脂止血颗粒进行治疗。基于大鼠体重、胰岛素抵抗稳态模型评估和胰岛素敏感性指数、血清脂肪因子水平以及组织病理学变化来评估玉脂止血颗粒的治疗效果。采用代谢组学和蛋白质组学方法寻找玉脂止血颗粒的作用途径。结果显示，玉脂止血颗粒可降低大鼠体重，提高胰岛素敏感性和芳香化酶活性，改善瘦素、脂联素等脂肪因子水平，减轻PCOS-IR大鼠的胰岛素抵抗、组织病理学变化和代谢紊乱。代谢组学结果显示，卵巢组织中有14种代谢物水平发生改变，这些代谢物与谷胱甘肽代谢和丙酮酸代谢密切相关。蛋白质组学结果表明，玉脂止血颗粒的治疗作用主要与脂肪因子、5'-单磷酸腺苷（AMP）激活的蛋白激酶（AMPK）、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）、叉头框蛋白O（FoxO）和雷帕霉素靶蛋白（mTOR）信号通路有关。蛋白质免疫印迹结果显示，与模型组相比，玉脂止血颗粒治疗可降低p-AMPK/AMPK和p-FoxO1/FoxO1水平，提高p-mTOR/mTOR水平，并上调重组葡萄糖转运蛋白4（GLUT4）的表达水平。玉脂止血颗粒可通过调节AMPK/mTOR/FoxO/GLUT途径平衡氨基酸代谢和丙酮酸代谢，维持卵巢环境的稳态，减轻胰岛素抵抗，从而治疗PCOS-IR。
