二甲双胍干预FFA诱发内质网应激介导的IR及β细胞凋亡的机制研究

苏晓萍; 李庆铃; 曾纪斌; 梁奇; 曹丽萍

文章摘要

苏晓萍，李庆铃，曾纪斌，梁奇，曹丽萍.二甲双胍干预FFA诱发内质网应激介导的IR及β细胞凋亡的机制研究[J].实用中西医结合临床,2021,21(17):1-5

二甲双胍干预FFA诱发内质网应激介导的IR及β细胞凋亡的机制研究

Study on the Mechanism of Metformin Intervention in FFA-induced Endoplasmic Reticulum Stress-mediated IR and β Cell Apoptosis*

DOI：

中文关键词: 二甲双胍游离脂肪酸内质网应激相关蛋白胰岛素抵抗 β细胞凋亡

英文关键词: Metformin Free fatty acid Endoplasmic reticulum stress related proteins Insulin resistance β Cell apoptosis

基金项目:深圳市宝安区科技基金计划基础项目（编号：2019JD299）

作者	单位
苏晓萍，李庆铃，曾纪斌，梁奇，曹丽萍	广东省深圳市宝安区中医院

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中文摘要:

目的：探究二甲双胍干预游离脂肪酸诱发内质网应激介导胰岛素抵抗与β细胞凋亡的机制。方法：应用游离脂肪酸喂养建立2型糖尿病大鼠模型，将建模大鼠随机分为二甲双胍组与模型组，二甲双胍组每天予200 mg/kg浓度二甲双胍，模型组每天予相同体积生理盐水，将正常喂养大鼠作为空白对照组，同样予相同体积生理盐水。三组均给药52 d，比较三组大鼠尾尖静脉血糖代谢、β细胞凋亡率、内质网应激指标信使核糖核酸水平、内质网应激指标蛋白表达水平。结果：模型组与二甲双胍组大鼠体质量、新β细胞功能指数均显著低于空白对照组（P＜0.05），空腹血糖、空腹胰岛素、胰岛素抵抗指数均显著高于空白对照组（P＜0.05）；二甲双胍组大鼠体质量、新β细胞功能指数均显著高于模型组（P＜0.05），空腹血糖、空腹胰岛素、胰岛素抵抗指数均显著低于模型组（P＜0.05）；模型组与二甲双胍组大鼠胰腺β细胞凋亡率均显著高于空白对照组（P＜0.05），二甲双胍组大鼠胰腺β细胞凋亡率显著低于模型组（P＜0.05）；模型组与二甲双胍组大鼠免疫球蛋白重链结合蛋白、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白等内质网应激指标信使核糖核酸水平均显著高于空白对照组（P＜0.05），二甲双胍组大鼠免疫球蛋白重链结合蛋白、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白等内质网应激指标信使核糖核酸水平均显著低于模型组（P＜0.05）；模型组与二甲双胍组大鼠胰腺组织磷酸化蛋白激酶B、蛋白激酶B、胰岛素受体β等内质网应激指标蛋白表达水平均显著低于空白对照组（P＜0.05），二甲双胍组各内质网应激指标蛋白表达均显著高于模型组（P＜0.05）。结论：二甲双胍可经由下调胰腺内质网应激相关指标信使核糖核酸水平，促进胰腺内质网应激相关蛋白表达，有效抑制游离脂肪酸所致胰岛素抵抗及β细胞凋亡。

英文摘要:

Objective: To investigate the mechanism of metformin intervention in free fatty acid-induced endoplasmic reticulum stress-mediated insulin resistance and β cell apoptosis. Methods: Free fatty acid was used to establish rat models of type 2 diabetes mellitus, and they were randomly divided into metformin group and model group. The metformin group was treated with 200 mg/kg of metformin every day, while the model group was treated with the same volume of normal saline every day. The rats fed routinely were taken as blank control group and treated with the same volume of normal saline. These three groups received 52 days of administration. The blood glucose metabolism of the tail apex vein, β-cell apoptosis rate, the mRNA level of the stress index of endoplasmic reticulum and the expression level of the protein of the stress index of endoplasmic reticulum were compared between the three groups. Results: The body mass and modified β-cell function index of the model group and the metformin group were significantly lower than those of the blank control group (P＜0.05), while the fasting blood glucose, fasting insulin and HOMA-IR were significantly higher than those in the blank control group (P＜0.05). The body mass and modified β-cell function index of the metformin group were significantly higher than those of the model group (P＜0.05), fasting blood glucose, fasting insulin and HOMA-IR were significantly lower than those of the model group (P＜0.05). The rat pancreas β cell apoptosis rate of the model group and the metformin group were significantly higher than the blank control group (P＜0.05), while this rate of the metformin group was significantly lower than that of model group (P＜0.05). The mRNA levels of ER stress indexes, such as immunoglobulin heavy chain binding protein, C/EBP cyclic adenosine monophosphate response element binding transcription factor homologous protein, in the model group and metformin group were significantly higher than those in the blank control group (P＜0.05), and these levels of the metformin group was significantly lower than that of model group (P＜0.05). Expression level of isoendoplasmic reticulum stress index protein such as phosphorylated protein kinase B, protein kinase B, insulin receptor β in the pancreatic tissue of rats in model group and metformin group were significantly lower than that in blank control group (P＜0.05), and these expression levels of the metformin group was significantly higher than that of model group (P＜0.05). Conclusion: Metformin can effectively inhibit FAA-induced IR and β-cell apoptosis through down-regulating pancreatic endoplasmic reticulum stress-related mRNAs, and promote the expression of pancreatic endoplasmic reticulum stress-related proteins.

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