玉屏风散调控IRS/PI3K/Akt通路对2型糖尿病大鼠肝脏胰岛素抵抗的作用机制  

Mechanism of Yupingfeng Powder on hepatic insulin resistance in type 2 diabetes mellitus rats by regulating IRS/PI3K/Akt pathway

作　　者：胡朝妙 廖晗禹 姜盛铭 张丽芳 马琪 HU Chao-miao;LIAO Han-yu;JIANG Sheng-ming;ZHANG Li-fang;MA Qi(College of Veterinary Medicine,Southwest University,Chongqing 402460,China)

机构地区：[1]西南大学动物医学院,重庆402460

出　　处：《中国中药杂志》2024年第12期3280-3287,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(32202849);重庆市自然科学基金项目(cstc2021jcyj-msxmX0982);重庆市大学生创新创业训练计划项目(S202310635385)。

摘　　要：基于胰岛素受体底物(IRS)/磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)通路研究玉屏风散对2型糖尿病(T2DM)大鼠的干预作用,探究玉屏风散改善T2DM大鼠肝脏胰岛素抵抗的潜在机制。采用高脂高糖饲料喂养联合腹腔注射链脲佐菌素建立T2DM大鼠模型。选取造模成功的大鼠分为模型组、阳性对照组和玉屏风散组,同时,另设空白组,分别给予相应药物灌胃治疗,模型组和空白组灌胃等量生理盐水。实验期间定期测定体质量、空腹血糖,实验末期测定葡萄糖耐量及胰岛素耐量。实验结束后测定血糖、胰岛素,血脂及相关肝脏功能指标水平;观察肝脏病理损伤变化,检测肝脏单胺氧化酶水平,qRT-PCR法检测IRS/PI3K/Akt通路相关基因mRNA表达量。结果显示,与模型组相比,玉屏风散组大鼠体质量增加;空腹血糖、空腹胰岛素、稳态模型评估指数降低;葡萄糖耐量及胰岛素耐量下面积降低;血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇含量降低,高密度脂蛋白胆固醇含量升高;肝脏单胺氧化酶水平降低;血清谷草转氨酶、谷丙转氨酶、碱性磷酸酶、总胆红素水平降低,总蛋白、白蛋白水平升高;苏木精-伊红(HE)染色显示肝细胞病理性损伤有所减轻。同时,与模型组相比,玉屏风散组大鼠肝脏IRS1、PI3K和Akt mRNA表达明显升高,白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)mRNA表达明显降低。以上表明玉屏风散可通过调控IRS/PI3K/Akt信号通路,调节糖脂代谢紊乱,提高胰岛素敏感性,改善肝脏胰岛素抵抗,进而发挥治疗T2DM的作用。Based on the insulin receptor substrate(IRS)/phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)pathway,the intervention effect of Yupingfeng Powder on type 2 diabetes mellitus(T2DM)rats was studied,and the potential mechanism of improving T2DM hepatic insulin resistance was explored.A T2DM rat model was established by feeding with high-fat and high-sugar feed combined with intraperitoneal injection of streptozotocin.Successfully modeled rats were selected and divided into a model group,a positive control group(MET),and a Yupingfeng Powder group.At the same time,a blank group was set up,and corresponding drugs were given by gavage.The model group and blank group were given an equal amount of physiological saline by gavage.During the experiment,body mass and fasting blood glucose were regularly measured,and glucose tolerance and insulin tolerance were measured at the end of the experiment.After the experiment,the levels of blood glucose,insulin,blood lipids,and related liver function indicators were measured;changes in liver pathological damage were observed,levels of liver monoamine oxidase were detected,and qRT-PCR was used to detect mRNA expression levels of IRS/PI3K/Akt pathway related genes.Compared with the model group,the Yupingfeng Powder group had an increase in body weight,a decrease in fasting blood glucose,fasting insulin,and steady-state model evaluation index,a decrease in the area under the curve of glucose tolerance and insulin tolerance tests,a decrease in serum total cholesterol,triglycerides,and low-density lipoprotein cholesterol content,and an increase in high-density lipoprotein cholesterol content.Compared with the model group,the Yupingfeng Powder group showed a decrease in liver monoamine oxidase levels,a decrease in serum aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,and total bilirubin levels,and an increase in total protein and albumin levels.Hematoxylin-eosin(HE)staining showed a reduction in pathological liver cell damage.Compared with the model group,the

关 键 词：玉屏风散 胰岛素抵抗 2型糖尿病 IRS/PI3K/Akt通路 

分 类 号：R285.5[医药卫生—中药学]