基于AMPK/GLUT4/GSK3β/PPARα信号通路研究地骨皮水提物改善2型糖尿病大鼠胰岛素抵抗的实验研究

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Abstract Objective To study on the improvement of insulin resistance (IR) in rats with type 2 diabetes mellitus (T2DM) was conducted based on AMPK/GLUT4/GSK3β/PPARα signaling pathway. Methods Sixty Wistar rats were divided into control group and high-fat experimental group (n = 50), and 40 rats which were successfully modeled and met the requirements of the model in the high-fat experimental group were divided into, model group, positive control group [Rosiglitazone 2 mg/(kg·d)], Cortex Lycii Radicis low dose group [5 mg/(kg·d)] and high dose group [10 mg/(kg·d)] by the random number table method, with 10 rats in each group. Each groups were given continuous administration for 6 weeks. Fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aminotransferase (AST) and alanine aminotransferase (ALT) levels of rats in each group were compared and liver morphology was observed. Protein mass concentration in liver was determined by BCA method. Results FBG levels in model group were higher than those in control group, while FBG levels in Cortex Lycii Radicis low dose group and Cortex Lycii Radicis high dose group were significantly lower than those in model group, with statistically significant differences (all P < 0.05). The levels of TC, TG and LDL-C in model group were higher than those in control group, while the levels of HDL-C were lower than those in control group, with statistically significant differences (all P < 0.05). After 6 weeks of intervention, the levels of TC, TG and LDL-C in Cortex Lycii Radicis low dose group and Cortex Lycii Radicis high dose group were lower than those in model group, while the levels of HDL-C were higher than those in model group, with statistically significant differences (all P < 0.05). The levels of ALT and AST in model group were higher than those in control group. After 6 weeks of intervention, the levels of ALT and AST in Cortex Lycii Radicis low dose group and Cortex Lycii Radicis high dose group were lower than those in model group, with statistically significant differences (all P < 0.05). HE staining showed clear hepatic lobule structure in the control group. In model group, the arrangement of hepatocytes was disordered and lipid vacuoles were obvious. The hepatic fat vacuoles of rats in Cortex Lycii Radicis high dose group were significantly reduced and the structural changes of hepatocytes and steatosis were significantly improved. Oil red O staining showed liver was significant accumulation of lipid droplets in the liver of rats in model group and was decreased lipid deposition in Cortex Lycii Radicis high dose group. The levels of p-AMPK, PPARα and GLUT4 of liver in model group were lower than those in control group, and the GSK3β levels were higher than those in control group, with statistically significant differences (all P < 0.05). The levels of p-AMPK, PPARα and GLUT4 of liver were significantly up-regulated and GSK3 levels were significantly down-regulated in Cortex Lycii Radicis high dose group (P < 0.05). Conclusion The FBG of T2DM rats can be significantly reduced by Cortex Lycii Radicis, improve dyslipidemia and liver pathological changes. It may up-regulate the expression of GLUT4 and PPARα protein and down-regulate the over-expression of GSK3β protein through AMPK signaling pathway to improve IR.

Key words： Cortex Lycii Radicis Type 2 diabetes mellitus model rats Insulin resistance AMP-activated protein kinase

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	YAO Huanhuan1 CHEN Ji1 CHEN Sisi1 ZHOU Diyi2

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YAO Huanhuan1 CHEN Ji1 CHEN Sisi1 ZHOU Diyi2. Experimental study on the improvement of insulin resistance in rats with type 2 diabetes mellitus with Cortex Lycii Radicis based on AMPK/GLUT4/GSK3β/ PPARα signaling pathway[J]. 中国医药导报, 2020, 17(5): 8-12.

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http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2020/V17/I5/8

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