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黄连素联合健脾益肾化浊方通过激活PI3K/AKT信号通路治疗肥胖型多囊卵巢综合征的作用机制研究

Study on the mechanism of action of berberine combined with Jianpi Yishen Huazhuo formulation in treating obese polycystic ovary syndrome by activating PI3K/AKT signaling pathway.

作者信息

Zhang Xiaojing, Ji Dejiang, Zhang Yan, Du Cuizhong, Liang Lijun, Ahmad Aqsa, Feng Yahong, Ye Gaxi

机构信息

Department of Gynecology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine and the Research Institute of Traditional Chinese Medicine, Ningxia, China.

Department of Acupuncture and Moxibustion, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine and the Research Institute of Traditional Chinese Medicine, Ningxia, China.

出版信息

Gynecol Endocrinol. 2025 Dec;41(1):2462068. doi: 10.1080/09513590.2025.2462068. Epub 2025 Feb 18.

DOI:10.1080/09513590.2025.2462068
PMID:39967331
Abstract

OBJECTIVES

This study aims to investigate the effects and potential mechanisms of berberine in conjunction with Jianpi Yishen Huazhuo formulation (JPYSHZF) on obese rats that serve as a model for polycystic ovary syndrome (PCOS).

METHODS

Letrozole combined with high-fat diet (HFD) was used to establish an overweight PCOS rat model. After successful modeling, each intervention group was monitored for 28 d. An oral glucose tolerance test (OGTT) is performed to assess glucose metabolism. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of sex hormones and serum levels of gastrointestinal hormones in rats. Biochemical analyzers were used to assess blood lipid levels. The protein expression levels of p38, PI3K, GLUT4, and AKT in ovarian tissue were demonstrated using Western Blotting (WB). Real-time fluorescence quantitative PCR (RT-qPCR) was used to measure the mRNA expression levels of p38, PI3K, GLUT4 and AKT in the same tissue. The morphological changes of ovarian tissue were observed using Hematoxylin-eosin (HE).

RESULTS

Treatment with berberine in conjunction with JPYSHZF has been shown to reduce serum testosterone T and luteinizing hormone (LH) levels while increasing serum follicle-stimulating hormone (FSH) and E2 levels. This combination therapy also decreases the LH/FSH ratio and ameliorates polycystic ovary-like pathological changes in the ovaries of rats with PCOS. Additionally, this treatment decreases serum TC, TG, and LDL-c levels while increasing HDL-c levels. It also reduces levels of GLU and Ghrelin while enhancing levels of CCK, PYY, and GLP-1. Furthermore, the relative 6 of PI3K and AKT proteins, as well as the mRNA levels of PI3K, GLUT4, and AKT, were found to be increased.

CONCLUSIONS

Berberine combined with JPYSHZF can improve the sex hormone levels, ovarian function, glucose and lipid metabolism levels, and gastrointestinal hormone levels in obese PCOS rats by activating the PI3K/AKT signaling pathway, thereby playing a role in treating obese PCOS.

摘要

目的

本研究旨在探讨黄连素联合健脾益肾化痰方(JPYSHZF)对作为多囊卵巢综合征(PCOS)模型的肥胖大鼠的影响及潜在机制。

方法

采用来曲唑联合高脂饮食(HFD)建立超重PCOS大鼠模型。成功建模后,对各干预组进行28天监测。进行口服葡萄糖耐量试验(OGTT)以评估葡萄糖代谢。采用酶联免疫吸附测定(ELISA)法测定大鼠性激素水平和胃肠激素血清水平。使用生化分析仪评估血脂水平。采用蛋白质印迹法(WB)检测卵巢组织中p38、PI3K、GLUT4和AKT的蛋白表达水平。采用实时荧光定量PCR(RT-qPCR)法检测同一组织中p38、PI3K、GLUT4和AKT的mRNA表达水平。采用苏木精-伊红(HE)染色观察卵巢组织形态学变化。

结果

黄连素联合JPYSHZF治疗可降低血清睾酮T和黄体生成素(LH)水平,同时提高血清促卵泡生成素(FSH)和E2水平。这种联合治疗还可降低LH/FSH比值,改善PCOS大鼠卵巢多囊样病理变化。此外,该治疗可降低血清总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-c)水平,同时提高高密度脂蛋白胆固醇(HDL-c)水平。它还可降低血糖(GLU)和胃饥饿素水平,同时提高胆囊收缩素(CCK)、肽YY(PYY)和胰高血糖素样肽-1(GLP-1)水平。此外,还发现PI3K和AKT蛋白的相对含量以及PI3K、GLUT4和AKT的mRNA水平升高。

结论

黄连素联合JPYSHZF可通过激活PI3K/AKT信号通路改善肥胖PCOS大鼠的性激素水平、卵巢功能、糖脂代谢水平和胃肠激素水平,从而发挥治疗肥胖PCOS的作用。

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