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目的通过观察结缔组织生长因子(CTGF)在糖尿病大鼠肾脏中表达的动态改变,探讨CTGF在糖尿病肾病发生发展中的作用。方法尾静脉内注射链脲佐菌素(STZ)诱导糖尿病大鼠模型。采用RT-PCR和Western blot检测1个月、3个月和6个月时糖尿病大鼠肾脏组织中CTGF的mRNA和蛋白的表达。光镜下观察糖尿病大鼠不同时期肾脏组织形态学的改变。结果糖尿病大鼠1个月、3个月和6个月与同期对照大鼠相比,肾脏CTGF的mRNA表达上调,分别为对照组的1.56倍、2.05倍和3.74倍(P<0.01);同时蛋白表达亦上调,分别为对照组的2.48倍、2.93倍和5.82倍(P<0.01);此外,糖尿病6个月大鼠的CTGF mRNA和蛋白的表达明显高于糖尿病1个月和3个月大鼠的表达水平(P<0.01)。组织形态学观察表明,糖尿病大鼠3个月时肾脏出现基膜增厚、肾小球扩张等糖尿病肾病早期的病理改变,随着病程的延长,病理改变越严重;6个月时出现肾小球硬化、肾间质纤维化等晚期的改变。结论糖尿病大鼠早期肾脏已存在CTGF基因表达上调,在糖尿病肾病的发展过程中,CTGF基因表达上调仍持续存在。因此,CTGF基因表达上调在糖尿病肾病的发生发展中起着重要作用。
Objective To investigate the dynamic changes of connective tissue growth factor (CTGF) expression in the kidney of diabetic rats and explore the role of CTGF in the development of diabetic nephropathy. Methods Rats were induced by streptozotocin (STZ) into the tail vein. The mRNA and protein expression of CTGF in kidney tissue of diabetic rats at 1 month, 3 months and 6 months were detected by RT-PCR and Western blot. The morphological changes of kidney in diabetic rats at different stages were observed under light microscope. Results Compared with the control rats in the same period, the expression of CTGF mRNA in kidney increased by 1.56 times, 2.05 times and 3.74 times respectively (P <0.01) in diabetic rats at 1 month, 3 months and 6 months. The expression of CTGF mRNA and protein in the 6-month-old diabetic rats was significantly higher than that of the diabetic patients at 1 month and 3 months (P <0.01) Rat expression level (P <0.01). Histopathological examination showed that the pathological changes of diabetic nephropathy such as thickening of basilar membrane and glomerular dilatation appeared in diabetic rats at 3 months. The pathological changes were more serious with the prolongation of the course of disease. At 6 months, Ball sclerosis, renal interstitial fibrosis and other late changes. Conclusion CTGF gene expression is up-regulated in the early stage of diabetic rats. Up-regulation of CTGF gene expression persists in the development of diabetic nephropathy. Therefore, the upregulation of CTGF gene plays an important role in the occurrence and development of diabetic nephropathy.