益肾祛浊方调节雌激素通路干预PCOS-IR大鼠脂代谢异常的研究  

Study on Yishen Quzhuo Formula regulating estrogen pathway to interfere with abnormal lipid metabolism in PCOS-IR rats

作　　者：尹谦 李美和 梁婧翘 李梦元 高征[1] 许昕[1] YIN Qian;LI Meihe;LIANG Jingqiao;LI Mengyuan;GAO Zheng;XU Xin(Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China)

机构地区：[1]首都医科大学附属北京中医医院,北京100010

出　　处：《中华中医药杂志》2023年第7期3329-3333,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81674010)。

摘　　要：目的:探究益肾祛浊方对多囊卵巢综合征合并胰岛素抵抗(PCOS-IR)大鼠脂代谢的影响和对雌激素信号通路的调节作用,揭示益肾祛浊方干预PCOS-IR的分子机制。方法:将大鼠随机分为空白组、模型组、益肾祛浊方组(益肾祛浊方10 g·kg^(-1)·d^(-1)灌胃)、西药组[二甲双胍50 mg·kg^(-1)·d^(-1)联合达英-35(醋酸环丙孕酮0.2 mg·kg^(-1)·d^(-1),炔雌醇3.5μg·kg^(-1)·d^(-1))]。以来曲唑1 mg·kg^(-1)·d^(-1)灌胃联合高脂饲料喂养法建立PCOS-IR模型。检测各组大鼠血清总胆固醇(TC)、甘油三酯(TG)水平,HE染色观察大鼠脂肪组织形态学改变;免疫组化法、Western Blot法、qPCR法检测大鼠脂肪组织中雌激素信号通路上经典蛋白(ESR1、MMP2、EGFR、MAPK3)及mRNA表达情况。结果:模型组大鼠TC、TG水平较空白组显著升高(P<0.01),脂肪细胞重度扩张;脂肪组织ESR1、MMP2、EGFR蛋白及mRNA表达显著升高,p-MAPK3蛋白表达显著降低(P<0.01)。益肾祛浊方干预后,大鼠TC、TG水平显著降低(P<0.01),脂肪细胞扩张程度改善;脂肪组织ESR1、MMP2、EGFR蛋白及mRNA表达显著降低,p-MAPK3蛋白表达显著升高(P<0.01),其效果与二甲双胍联合达英-35作用相当。结论:益肾祛浊方可能通过调节雌激素信号通路改善PCOS-IR模型大鼠脂代谢异常,恢复脂肪组织正常形态。Objective:To explore the effects of Yishen Quzhuo Formula on lipid metabolism and regulation of estrogen signaling pathway in rats with polycystic ovary syndrome-insulin resistance(PCOS-IR),and to reveal the molecular mechanism of Yishen Quzhuo Formula’s intervention on PCOS-IR.Methods:The rats were randomly divided into blank group,model group,Yishen Quzhuo Formula group(Yishen Quzhou Fomula 10 g·kg^(-1)·d^(-1))and western medicine group[metformin 50 mg·kg^(-1)·d^(-1)+Diane-35(cyproterone acetate 0.2 mg·kg^(-1)·d^(-1),ethinyloestradiol 3.5μg·kg^(-1)·d^(-1))].PCOS-IR model was established by letrozole gavage combined with high fat feed.The serum total cholesterol(TC)and triglyceride(TG)levels of each group were detected,and the morphological changes of adipose tissue were observed by HE staining.Immunohistochemistry,Western Blot and qPCR were used to detect the expression of classical proteins(ESR1,MMP2,EGFR and MAPK3)and mRNA in the estrogen signaling pathway in rat adipose tissue.Results:The levels of TC and TG in model group were higher than those in blank group(P<0.01),and the adipocytes were severely dilated.The protein and mRNA expressions of ESR1,MMP2 and EGFR were increased in adipose tissue,while the expression of p-MAPK3 was decreased(P<0.01).The results showed that total cholesterol and triglyceride levels were decreased(P<0.01),and adipocyte expansion was improved.The protein and mRNA expressions of ESR1,MMP2 and EGFR were decreased in adipose tissue,while the expression of p-MAPK3 was increased(P<0.01),which was similar to the effect of metformin combined with Diane-35.Conclusion:Yishen Quzhuo Formula may improve abnormal lipid metabolism and restore normal form of adipose tissue in PCOS-IR model rats by regulating estrogen signaling pathway.

关 键 词：多囊卵巢综合征 胰岛素抵抗 益肾祛浊方 雌激素信号通路 脂代谢异常 

分 类 号：R285.5[医药卫生—中药学]