罗格列酮减轻2型糖尿病大鼠血管内皮功能受损

摘要

目的 观察2型糖尿病大鼠血清内皮素(ET)和一氧化氮(NO)水平、主动脉病理变化、在主动脉的内皮型一氧化氮合酶(eNOS)蛋白和mRNA表达及罗格列酮的干预作用.方法 将大鼠随机分为对照组、高脂组、糖尿病组和罗格列酮组,每组20只.制备2型糖尿病大鼠模型后,罗格列酮治疗组4 mg/kg·d灌胃给药,于治疗6周和12周时检测血糖、ET、NO及光镜下主动脉的病理变化;用Western blot和real-time PCR检测主动脉的eNOS蛋白和mRNA表达.结果 1)与对照组比较,高脂组、糖尿病组及罗格列酮治疗组ET升高,NO降低(P<0.01).12周时糖尿病组较高脂组和罗格列酮治疗组ET升高,NO降低(P<0.05).糖尿病组NO水平在12周时比6周时明显下降(P<0.05).2)12周时高脂组、糖尿病组和罗格列酮组大鼠主动脉出现不同程度病理改变.3)6周和12周时,与对照组比较,高脂组、糖尿病组和罗格列酮组主动脉eNOS的蛋白和mRNA表达下调(P<0.01);糖尿病组较罗格列酮组主动脉eNOS的蛋白表达下调(P<0.01).结论 罗格列酮可以缓解糖尿病组大鼠血管内皮功能受损.%To observe metabolic abnormalities, histology changes and eNOS expression of aorta in type 2 diabetes rat.And to observe intervention effect of rosiglitazone.Methods 80 male Wistar rats were randomized to control group, high diet group, diabetes group, and rosiglitazone treatment group (diabetes plus rosiglitazone treatment).Type 2 diabetes models were developed and rosiglization group was treated with rosiglitazone .Six weeks and twelve weeks after treatment with rosiglitazone, blood glucose, endothlin and nitric oxide were tested.Histology changes of aorta in different groups were observed under microscopy .Meanwhile the protein and mRNA expression of eNOS in aorta were examined.Results 1)Compared with control group, ET in high fat diet group, diabetes group and rosiglitazone group increased significantly , and the level of NO decreased significantly at 6 week and 12 week.At 12 week, ET in diabetes group increased, and NO decreased significantly than that of high fat diet group and rosiglitazone group.2)Histology changes were observed in high fat diet group , diabetes group and rosiglitazone group at 12 week.3)Compared with control group, protein and mRNA expression in high fat diet group , diabetes group and rosiglitazone group were down regulated at 6 week and 12 week.And protein expression in diabetes group was down regulated than that in rosiglitazone group .Conclusions Rosiglization can ease the endothelial dysfunction in type 2 diabetes rat.