TRPC6在糖尿病大鼠模型肾损害中的作用及其意义

Study of the Significance and Role of TRPC6 in Diabetic Rats with kidney damage

目的观察瞬时受体电位阳离子通道-6(transient receptor potential canonical-6,TRPC6)在链脲佐菌素(streptozotocin,STZ)诱导糖尿病(diabetes mellitus,DM)大鼠模型中的表达,并探讨TRPC6在DM肾损害中的作用及意义。方法雄性SD大鼠70只,随机分为正常对照组(normal control group,NCG)15只和实验组(experimental group,EG)55只。实验组采用STZ 70mg/kg单次腹腔注射方式建立DM大鼠模型,按照成模标准去除未成模大鼠。监测各组大鼠的空腹血糖(fasting blood glucose,FBG)、尿蛋白(urine protein,UP)以及肾功能;分别于2、4、8周处死各组大鼠,收取肾脏留做病理及免疫组化;分别对TRPC6与尿蛋白以及肾功能做相关性分析。结果与正常对照组相比,DM组的FPG显著增加(P<0.05),而DM组各时点间的血糖水平无明显差异;与正常对照组相比,DM组4、8周大鼠的肌酐、尿素氮以及尿蛋白水平显著增加,差异有统计学意义(P<0.05),而DM组2周大鼠的肌酐、尿素氮以及尿蛋白水平无明显增加(P>0.05)。与正常对照组相比,DM组的TRPC6表达明显增加,并随着造模时间的延长而继续增加,差异有统计学意义(P<0.05)。DM组大鼠TRPC6的表达水平分别与肌酐(r=0.745,P<0.05)、尿素氮水平(r=0.695,P<0.005)、尿蛋白水平(r=0.713,P<0.005)呈正相关。结论高血糖可诱导DM大鼠模型肾脏高表达TR-PC6,TRPC6可能参与了糖尿病大鼠模型蛋白尿及肾损害的发生发展。

Objective To analysis and explore the significance and role of transient receptor potential canonical-6 in the pathogenesis of diabetes mellitus by observation the general expression of TRPC6 in streptozotocin induced diabetic rats. Methods 70 male SD rats were randomly divided into normal control group （n=15） and experimental group （n= 55）. Experimental group were treated with an intraperitoneal injection of STZ 70 mg/kg to establish the model of DM. After the injection of STZ, the rats of fasting blood glucose of the experimental group does not meet to the standard of model were excluded. The level of the fasting blood glucose （FBG）, urine protein （UP） and renal function were moni-tored in each group; rats in each group were sacrificed at 2, 4 and 8 weeks, respectively; kidneys were harvested for pathology and immunohistochemistry; correlation analysis were done between TRPC6 and urine protein as well as renal function. Results The level of FBG were significantly higher compared with normal control group （P%0.05） ; there was no significant difference in FBG among each time point. Compared with normal control group, the creatinine, urea nitrogen and urinary protein level of DM group 4 weeks and 8 weeks were significantly increased （P（0.05）. However, the creatinine, urea nitrogen and urinary protein level of DM group 2 weeks were not significantly increased（P;〉0. 05）. Compared with normal control group, the expression of TRPC6 in DM group was significantly increased and continue to increase with time （P〈0.05）. The expression of TRPC6 in DM rats was positively correlated with the level of creatinine （r=0. 745, P〈0.05）, the level of urea nitrogen （r=0. 695, P%0. 005） and the level of urine protein （r=0. 713, P; 0. 005）. Conclusion Hyperglycemia can induce high expression of TRPC6 in the rat model of DM kidney, TRPC6 may be involved in the development of proteinuria and renal damage in diabetic rat model.