基于IL-6/IL-6R信号通路探讨黄连温胆汤对多囊卵巢综合征伴胰岛素抵抗的影响OA
Investigation on the Effect of Huanglian Wendan Decoction on Polycystic Ovary Syndrome with Insulin Resistance Based on IL-6/IL-6R Signaling Pathway
目的 基于IL-6/IL-6R通路探讨黄连温胆汤调控多囊卵巢综合征(PCOS)伴胰岛素抵抗的作用机制.方法 SPF级雌性SD大鼠66只,随机选择11只为空白组,其余55只采用脱氢表雄酮构建PCOS大鼠模型,造模成功大鼠随机分为模型组、二甲双胍组和黄连温胆汤低、中、高剂量组.黄连温胆汤低、中、高剂量组分别灌胃2.5、5.0、10.0 g/kg黄连温胆汤水煎液,二甲双胍组灌胃90 mg/kg二甲双胍,空白组和模型组灌胃等量纯水.观察大鼠一般状况、动情周期及卵巢的形态学变化;HE染色观察病理变化;透射电镜观察卵巢颗粒细胞线粒体超微结构;生化检测空腹血糖(FBG)、血清胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR);检测血清IL-6水平;Western blot测定IL-6、IL-6R、GLUT4、Collagen Ⅰ和α-SMA蛋白表达情况.结果 与空白组比较,模型组大鼠失去规律动情周期;空腹血糖、血清胰岛素含量和胰岛素抵抗指数增高(P<0.01);卵巢组织中可见较多闭锁小卵泡;透射电镜显示线粒体形态和数目发生变化;血清IL-6含量升高(P<0.01);IL-6、IL-6R、Collagen Ⅰ、α-SMA蛋白表达增高(P<0.01),GLUT4蛋白表达降低(P<0.01).与模型组比较,各给药组大鼠卵巢闭锁卵泡数量减少,可见成熟卵泡及黄体;线粒体结构损伤程度减轻;空腹血糖、血清胰岛素含量和胰岛素抵抗指数降低(P<0.05,P<0.01);血清IL-6含量降低(P<0.01);GLUT4蛋白表达增加(P<0.05,P<0.01);二甲双胍组和黄连温胆汤中、高剂量组IL-6、IL-6R、Collagen Ⅰ、α-SMA蛋白表达降低(P<0.01,P<0.05).结论 黄连温胆汤能够改善PCOS大鼠胰岛素抵抗及卵巢纤维化,其作用机制可能与调控IL-6/IL-6R信号通路及调节GLUT4相关.
Objective To investigate the mechanism of action of Huanglian Wendan Decoction in regulating insulin resistance in polycystic ovary syndrome(PCOS)with insulin resistance through IL-6/IL-6R pathway.Methods Of the 66 SPF female Sprague-Dawley rats,11 were randomly assigned to the blank group.The remaining 55 rats were used to establish a PCOS model by dehydroepiandrosterone induction.The successful modeling rats were randomly divided into model group,metformin group,low-,medium-and high-dose Huanglian Wendan Decoction groups.The low-,medium-and high-dose Huanglian Wendan Decoction groups were given Huanglian Wendan Decoction at doses of 2.5,5.0,and 10.0 g/kg by gavage,respectively.The metformin group was given metformin at a dose of 90 mg/kg by gavage,while blank group and model group were given the same amount of pure water by gavage.The general condition,estrous cycle and ovarian morphological changes of rats were observed.HE staining was used to observe the pathological changes;transmission electron microscopy was used to observe the ultrastructure of mitochondria in ovarian granulosa cells;biochemical assays were performed to measure fasting blood glucose(FBG)and fasting insulin(FINS)levels,from which the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated,serum IL-6 levels were also determined;protein expression levels of IL-6,IL-6R,Collagen Ⅰ,and α-SMA were determined by Western blot analysis.Results Compared with the blank group,the rats in the model group lost regular estrous cycle.FBG,FINS content and insulin resistance index were increased(P<0.01);and more atresia small follicles were seen in ovarian tissue.Transmission electron microscopy showed changes in mitochondrial morphology and number;the content of IL-6 was increased(P<0.01),protein expression levels of IL-6,IL-6R,GLUT4,Collagen Ⅰ and α-SMA were increased(P<0.01),and the expression of GLUT4 protein was decreased(P<0.01).Compared with the model group,all treatment groups exhibited a reduction in the number of atretic follicles in the ovaries,along with the presence of mature follicles and corpus luteum.Furthermore,the degree of mitochondrial structural damage was markedly alleviated.FBG,FINS content and insulin resistance index were decreased(P<0.05,P<0.01);the content of IL-6 was decreased(P<0.01),and the expression of GLUT4 protein was increased(P<0.05,P<0.01);protein expression levels of IL-6,IL-6R,Collagen Ⅰ and α-SMA in metformin group,medium-and high-dose Huanglian Wendan Decoction groups were decreased(P<0.01,P<0.05).Conclusion Huanglian Wendan Decoction can improve insulin resistance and ovarian fibrosis in PCOS rats,its mechanism of action may be related to the regulation of IL-6/IL-6R signaling pathway and the regulation of GLUT4.
何瑞琪;周丽;张小花;万文文;黄灿灿
无锡市第二人民医院,江苏 无锡 214000南通市中医院,江苏 南通 226000甘肃中医药大学,甘肃 兰州 730000甘肃中医药大学,甘肃 兰州 730000南通市中医院,江苏 南通 226000
黄连温胆汤多囊卵巢综合征胰岛素抵抗IL-6/IL-6R纤维化
Huanglian Wendan DecoctionPolycystic ovary syndromeInsulin resistanceIL-6/IL-6RFibrosis
《中医药信息》 2026 (10)
28-34,7
兰州市科技计划项目(2024-9-70)
评论