结缔组织生长因子在糖尿病肾病发生发展中的作用

目的 动态观察大鼠糖尿病肾病(DN)的不同阶段肾皮质结缔组织生长因子(CTGF)表达的变化及其与肾功能及肾组织形态学变化的相关性,探讨尿液中CTGF含量的检测作为DN诊断指标的意义.方法 以链脲佐菌素(STZ)诱导糖尿病大鼠为研究对象.63只大鼠分为糖尿病组33只和对照组30只.应用逆转录聚合酶链反应、免疫组织化学及蛋白质印迹法研究在糖尿病的不同时期肾皮质CTGF表达的动态变化,并研究其与DN早期肾肥大、ECM的聚积及后期肾小球硬化及肾间质纤维化之间的关系,同时以ELISA法检测糖尿病大鼠尿液中CTGF含量.结果 糖尿病大鼠肾皮质mRNA及CTGF蛋白质表达2周时开始增加,12周时达高峰,分别为(0.905±0.028)、(0.802±0.028),为正常对照组的4.38倍和9.97倍(均P＜0.05);其表达早期出现在肾小球,而后随着病程的发展出现于肾小管间质区域.相关性分析显示CTGF的表达与肾指数、肾小球体积、系膜基质指数、肾小管间质纤维化程度呈正相关(均P＜0.01);糖尿病大鼠尿液中CTGF的含量随着病程的发展逐渐升高,最高为(277.679±10.372)ng/L,与24h尿微量白蛋白、BUN、Cr呈正相关(均P＜0.01).结论 CTGF表达的增加贯穿了DN发病的整个过程,早期介导了肾肥大,肾小球ECM的积聚,晚期又介导了肾小球硬化及肾小管间质纤维化的发生;尿液CTGF的检测可以作为DN诊断的一个指标.

Effect of connective tissue growth factor in different phase of diabetic nephropathy

Objective To investigate the effect of connective tissue growth factor(CTGF) in different phase of streptozotocin(STZ) -induced diabetic nephropathy and the significance of examination of urine CTGF as one of the diabetic nephropathy(DN) diagnostic index. Methods STZ was used to induce diabetic rat model. Then the changes of CTGF expression in the kidney cortex at different phase of diabetes were examined. The relationship between CTGF expression and renal hypertrophy, the extracellular matrix (ECM) accumulation, diabetic glomerulosclcrosis and interstitial fibrogenesis were studied. Enzyme-linked immunoabsorbent assay was performed to examine the change of urine CTGF. Results Renal cortex CTGF expression increased at the second week of diabete onset and gradually increased along with the course of diabetes and reached peak at 12th week (P ＜ 0.05). The expression appeared in renal glomerulus in the early phase of DN and also appeared in renal tubular interstitial tissue in the later period. The relevant analysis demonstrated positive correlation between the expression of CTGF and the renal index, renal glomerular volume, mesangial matrix index and fibrosis degree of renal tubule tubular interstitial fibrogenesis (P ＜ 0. 01). The diabetic rat urine CTGF content increased (P ＜ 0. 01) along with the course of diabetes,which showed a positive correlation with urine MA, BUN and Cr (P ＜ 0.01). Conclusions CTGF plays a vital role in the DN developing process. Its expression increases through the whole process of DN. In the early time. CTGF mediates the renal hypertrophy and the glomerular ECM accumulation, and in the later period it also mediates diabetic glomerulosclerosis and interstitial fibrogenesis. The examination of urine CTGF content can be one of the DN diagnostic index.