EGCG通过调节GLUT4移位改善2型糖尿病大鼠海马胰岛素抵抗

EGCG improves hippocampal insulin resistance in rats with type 2 diabetes by modulating translocation of GLUT4

目的:探讨表没食子儿茶素没食子酸酯(EGCG)通过葡萄糖转运体4(GLUT4)转位改善2型糖尿病大鼠海马胰岛素抵抗,保护2型糖尿病大鼠的认知功能。方法:按照处理方式不同将50只大鼠随机分为正常组(con组)、糖尿病组(m组)、二甲双胍组(met组)、EGCG低剂量组(EL组)、EGCG高剂量组(EH组)组,每组各10只,除con组外,其余各组高脂饲养1个月后腹腔注射链脲佐菌素(STZ)制备2型糖尿病SD大鼠模型。met组给予二甲双胍治疗;EL组及EH组给予EGCG治疗;con组及m组均灌服生理盐水0.1 mL/kg,各组均治疗8周。Morris水迷宫实验后,处死大鼠,取海马,并收集血液。对比各组大鼠空腹血糖(FBG)、空腹血清胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、糖化血红蛋白水平。采用HE染色法观察海马结构;通过免疫组化法检查海马PM-GLUT4表达;通过Western blot检测海马组织总GLUT4(total GLUT4,T-GLUT4)和质膜GLUT4(PM-GLUT4)的表达情况。结果:与con组比较,m组大鼠FBG、FINS、HOMA-IR、糖化血红蛋白均升高(P<0.05)。与m组比较,met组、EL组及EH组FBG、FINS、HOMA-IR、糖化血红蛋白均降低(P<0.05)。HE染色结果显示,met组、EL组及EH组海马组织损伤降低。免疫组化结果显示,与con组比较,m组GLUT4蛋白表达水平下降;与m组比较,met、EL及EH组GLUT4蛋白表达水平均上升。Western blot结果显示,与con组比较,m组PM-GLUT4蛋白表达水平下降(P<0.05);与m组比较,met组、EL组及EH组PM-GLUT4蛋白表达水平均上升(P<0.05)。结论:EGCG通过增加GLUT4转位,缓解2型糖尿病诱发的大鼠海马胰岛素抵抗,对海马组织结构和功能起到保护作用。

Objective:To investigate whether epigallocatechin gallate can improve hippocampal insulin resistance in type 2 diabetic rats by influencing glucose transporter 4,thereby protecting cognitive function in type 2 rats.Methods:50 rats were divided into normal group(con group),diabetes group(m group),metformin group(met group),low dose EGCG group(EL group),and high dose EGCG group(EH group)according to different treatment methods,with 10 rats in each group.Except con group,the other groups were intraperitoneally injected with streptozotocin(STZ)after 1 month of high-fat feeding to prepare the type 2 diabetes SD rat model.The met group was treated with metformin,EL and EH groups were treated with EGCG,both the con and m groups were given 0.1 mL/kg of physiological saline by gavage,and each group was treated for 8 weeks.After Morris water maze experiment,the rats were executed and blood and hippocampal tissue were collected.The levels of fasting blood glucose(FBG),fasting serum insulin(FINS),insulin resistance index(HOMA-IR),and glycated hemoglobin of rats were comppared in each group.HE staining method was used to observe the hippocampal structure,the serum levels of fasting blood glucose,fasting serum insulin and glycosylated hemoglobin were measured by biochemical tests.The expression of PM-GLUT4 and T-GLUT4 were detected by Western blot,PM-GLUT4 was detected by immunohistochemistry.Results:Compared with con group,the serum levels of FBG,FINS,HOMA-IR and glycosylated hemoglobin in the m group were increased(P<0.05).Compared with m group,the serum levels of FBG,FINS,HOMA-IR and glycosylated hemoglobin in met,EL and EH groups were increased(P<0.05).The HE staining results showed a decrease in hippocampal tissue damage in the met,EL,and EH groups.The immunohistochemical results showed that compared with the con group,the expression level of GLUT4 protein in group m decreased,compared with group m,the expression levels of GLUT4 protein increased in met,EL,and EH groups.Western blot results showed that compared with the con group,the expression level of PM-GLUT4 protein in group m decreased(P<0.05),compared with group m,the expression levels of PM-GLUT4 protein increased in met group,EL group,and EH groups(P<0.05).Conclusion:EGCG improves hippocampal insulin resistance(IR)in rats with type 2 diabetes by increasing GLUT4 translocation,providing protection for hippocampal tissue structure and function.