Hu Chao-Miao, Liao Han-Yu, Jiang Sheng-Ming, Zhang Li-Fang, Ma Qi
College of Veterinary Medicine, Southwest University Chongqing 402460, China.
Zhongguo Zhong Yao Za Zhi. 2024 Jun;49(12):3280-3287. doi: 10.19540/j.cnki.cjcmm.20240220.401.
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 Yupingfeng Powder group showed a significant increase in the mRNA expression levels of IRS1, PI3K, and Akt in the liver of rats, as well as a significant decrease in the mRNA expression levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α). This indicates that Yupingfeng Powder can regulate the IRS/PI3K/Akt signaling pathway and glucose and lipid metabolism disorders, increase insulin sensitivity, improve hepatic insulin resistance, and thus play a therapeutic role in T2DM.
基于胰岛素受体底物（IRS）/磷酸肌醇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，探讨其改善T2DM肝脏胰岛素抵抗的潜在机制。通过高脂高糖饲料喂养结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（MET）和玉屏风散组。同时设空白组，采用灌胃给予相应药物。模型组和空白组灌胃等量生理盐水。实验期间定期测量体质量和空腹血糖，实验结束时检测葡萄糖耐量和胰岛素耐量。实验结束后，检测血糖、胰岛素、血脂及相关肝功能指标水平；观察肝脏病理损伤变化，检测肝脏单胺氧化酶水平，采用qRT-PCR检测IRS/PI3K/Akt通路相关基因的mRNA表达水平。与模型组比较，玉屏风散组体质量增加，空腹血糖、空腹胰岛素及稳态模型评估指标降低，葡萄糖耐量和胰岛素耐量试验曲线下面积减小，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。与模型组比较，玉屏风散组肝脏单胺氧化酶水平降低，血清天冬氨酸氨基转移酶、丙氨酸氨基转移酶、碱性磷酸酶和总胆红素水平降低，总蛋白和白蛋白水平升高。苏木精-伊红（HE）染色显示肝细胞病理损伤减轻。与模型组比较，玉屏风散组大鼠肝脏IRS1、PI3K和Akt的mRNA表达水平显著升高，白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的mRNA表达水平显著降低。这表明玉屏风散可调节IRS/PI3K/Akt信号通路及糖脂代谢紊乱，增加胰岛素敏感性，改善肝脏胰岛素抵抗，从而对T2DM发挥治疗作用。
