小檗碱对2型糖尿病大鼠肾脏GLUT1表达的影响

The effect of berberine on the expression of glucose transporter 1 in the kidney of type 2 diabetes mellitus rats

目的探讨小檗碱(Berberine,BBR)对2型糖尿病(type2 diabetes mellitus,T2DM)大鼠肾脏葡萄糖转运蛋白1(glucose transporter protein1,GLUT1)表达的影响及其对肾保护作用的机制,为临床用其防治糖尿病肾病打下理论基础。方法 45只健康雄性SD大鼠适应性喂养1周后随机抽取10只作为正常对照组(control,CON组),给予普通饲料。其余大鼠高脂高糖喂饲2个月后经尾静脉注射链脲佐菌素(streptozotocin,STZ)建立2型糖尿病大鼠模型。而后将成模大鼠随机分为糖尿病模型组(Model,DM组)13只、小檗碱治疗组(Berberine,BBR组)13只,给予相应处理8周后,检测各组大鼠体重(BW)、肾指数(KW/BW)、空腹血糖(FBG)、血总胆固醇(TC)、血总甘油三酯(TG)、血肌酐(Scr)、血尿素氮(BUN)量,免疫组织化学法和免疫蛋白印记法(Western-blotting)去定性和定量检测大鼠肾组织中GLUT1的表达。结果檗碱治疗组一般情况、生化指标变化均优于糖尿病模型组;模型组大鼠肾皮质GLUT1的表达较正常对照组显著增高(P<0.01);BBR组GLUT1的表达较模型组明显降低(P<0.01)。结论小檗碱有良好的降血糖、降血脂作用;小檗碱对2型糖尿病大鼠肾脏有明显保护作用,其机制可能与其下调GLUT1的表达,调节细胞外基质的生成与降解,延缓肾脏纤维化进程有关。

Objectives To investigate the effect of berberine on the expression of GLUT1 in the kidney of type 2 diabetes mellitus rats,and the mechanism of the protective effect of berberine on kidney,which can be useful for the clinical application to prevent and cure diabetic nephropathy.Methods 45 healthy male SD rats were adaptively fed for one week,and then ten were randomly selected from them as the normal control group,which were given ordinary feed.The remaining rats were fed with high-lipoglucose food for two monthes and injected STZ through caudal vein to establish the type 2 diabetes mellitus model.The model rats,were randomly divided into 2 groups：diabetic model group（DM group,13） and berberine treatment group（BBR group,13）.After approciate treatment for 8 weeks,each group＇s BW,KW/BW,FBG,TC,TG,Scr and BUN were measured,and the expression of GLUT1 was qualitatively and hemi-quantitatively detected by the methods of immune Western blot and immunohistochemistry.Results The general condition and the changes of biochemical indicators of the BBR group were superior to those of the DM group;compared with the normal control group,the GLUT1 expression of the DM group remarkably increased（P0.01）;compared with the the DM group,the GLUT1 expression of the BBR group strikingly decreased（P0.01）.Conclusions Berberine can effectively decrease blood sugar and blood fat.In addition,Berberine can also distinctly protect the kidneys of the rats of the type 2 diabetes mellitus,the mechanism of which are realted to decreasing the expression of GLUT1 and TGF-β1,regualting the generation and degradation of extracellular matrix,and putting off the process of kidney fibrosis.