TGF-β1和CTGF在大鼠肾小球硬化模型中的表达及意义  

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

作　　者：张瑶[1] 于力[1] 张蕾[1] 张建青 

机构地区：[1]广州医学院附属市一人民医院儿科,广州510180 [2]广东省广州市番禺区何贤纪念医院儿科,511400

出　　处：《广东医学》2010年第6期671-674,共4页Guangdong Medical Journal

基　　金：广东省自然科学基金项目(编号:5000424);广州市科技攻关计划项目(编号:2006Z3-E0231);广州市番禺区科技攻关项目(编号:2007-Z-78-1)

摘　　要：目的观察大鼠肾小球硬化模型转化生长因子β1(transforming growth factor-beta 1,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只大鼠随机分成对照组和模型组,每组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24 h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、8周24 h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、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(ex-tracellular 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。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.

关 键 词：转化生长因子-Β1 结缔组织生长因子 肾小球硬化 大鼠 

分 类 号：R692.202[医药卫生—泌尿科学]