TGF-β1和CTGF在大鼠肾小球硬化模型中的表达及意义

目的 观察大鼠肾小球硬化模型转化生长因子β1（transforming growth factor- beta1，TGF-β1）和结缔组织生长因子（connective tissue growing factor，CTGF）的表达，探讨其与肾小球硬化病变发生发展的关系。 方法 60只大鼠随机分成2组：对照组、模型组，每组共30只。模型组采用尾静脉注射阿霉素方法建立阿霉素肾病模型。检测各组大鼠24h尿蛋白定量及血清肾功能指标。观察各组大鼠肾组织病理学改变。采用免疫组织化学及荧光定量PCR方法检测肾组织TGF-β1、CTGF蛋白和mRNA的表达水平。 结果 ①模型组于第2、4、6和8周尿蛋白定量均高于同期对照组，差异有统计学意义（p<0.01）。第2、4、6和8周时模型组血尿素氮及肌酐水平均高于同期对照组（p<0.05）。②病理检查提示随时间延长，病变进展。③模型组第4、6周TGF-β1和CTGF免疫组化半定量分析结果均高于同期对照组（p<0.01）。④模型组于第2、4、6、8周TGF-β1和CTGF mRNA表达均高于同期对照组（p<0.05）。与TGF-β1表达趋势相比，CTGF蛋白及mRNA表达高峰出现时间均延迟。结论 TGF-β1和CTGF的过度表达是肾小球硬化发生发展的重要因素。CTGF可能作为TGF-β1的下游效应分子，共同促进细胞外基质（extracellular matrix，ECM）的积聚，造成肾小球硬化。阻断其表达可能为肾小球硬化提供新的治疗手段。 【关键词】 TGF-β1；CTGF；肾小球硬化；大鼠

Expression and implication of TGF-β1 and CTGF in rat glomerulosclerosis model

Objective To study the expression of TGF-β1 and CTGF in rat glomerulosclerosis model,and to investigate their relationship with the development of glomerulosclerosis. Methods Sixty rats were randomly assigned into control group (n=30) and model group (n=30). Glomerulosclerosis model was created via intravenous injection of adriamycin. The levels of 24 h urine protein (Upr),serum creatinine (sCr),blood urea nitrogen (BUN) and serum cholesterol (Ch) were examined. The renal morphological changes were observed under a microscope. The expression levels of TGF-β1 and CTGF in renal tissue were assessed using immunohistochemical method and fluorescent quantitation PCR,respectively. Results 24 h Upr,BUN and sCr significant increased at 2,4,6 and 8 week in the model group. The protein and mRNA expression levels of TGF-β1 and CTGF significantly increased in model group. The expression peak of CTGF tended to appear after TGF-β1. Conclusion The TGF-β1 and CTGF are important factors in the development of glomerulosclerosis. CTGF may play as a downstream molecule of TGF-β1 and promote the accumulation of ECM,which results in glomerulosclerosis. Blocking the expressions of TGF-β1 and CTGF would provide novel therapy for glomerulosclerosis.