肾疏宁对肾小球硬化大鼠肾小球系膜细胞表型转化的作用  

Study of the Effects of Shenshuning Mixture on Phenotypic Modulation of Mesangial Cell in Glomerulosclerosis Rats

作　　者：张丽芬[1] 黄文政[2] 

机构地区：[1]北京中医药大学东直门医院肾病内分泌科 [2]天津中医学院第一附属医院肾病科

出　　处：《首都医科大学学报》2007年第2期206-211,共6页Journal of Capital Medical University

基　　金：天津市自然科学基金(023611511)资助项目

摘　　要：目的观察中成药复方肾疏宁对肾小球硬化模型大鼠肾小球系膜细胞表型转化的作用,探讨肾疏宁防治肾小球硬化的作用机制。方法采用单侧肾切除并阿霉素尾静脉注射的方法建立大鼠肾小球硬化模型。用数字表法将SD大鼠随机分为假手术组、模型组、模型组+肾疏宁治疗组和模型组+苯那普利治疗组,共观察8周。用免疫组织化学染色法观察大鼠肾小球内α-平滑肌肌动蛋白(alpha smooth muscle actin,α-SMA)和转化生长因子-β1(transforming growth factor-β1,TGF-β1)的表达,用病理图像分析软件检测肾小球内α-SMA和TGF-β1染色阳性面积/肾小球毛细血管襻面积的改变。同时观察肾疏宁对肾小球硬化大鼠体质量、尿蛋白、血白蛋白、尿素氮、肌酐的影响。结果假手术组大鼠肾小球内未见α-SMA表达,可见TGF-β1少量表达;模型组大鼠肾小球内α-SMA和TGF-β1显著表达,与假手术组比较,差异有统计学意义(P<0.01);血白蛋白、总蛋白明显降低,与假手术组相比,差异有统计学意义(P<0.01);尿蛋白、血尿素氮、肌酐明显升高,与假手术组相比,差异有统计学意义(P<0.01)。肾疏宁治疗组和苯那普利治疗组24h尿蛋白排泄量、血尿素氮、肌酐明显降低,与模型组相比,差异有统计学意义(P<0.01)。肾小球内α-SMA阳性面积/肾小球毛细血管襻面积和TGF-β1阳性面积/肾小球毛细血管襻面积显著减少,与模型组比较差异有统计学意义(P<0.01)。相关性分析显示α-SMA和TGF-β1呈显著正相关(r=0.637,P<0.01)。结论肾疏宁可抑制肾小球系膜细胞表型转化,减少肾小球内固有细胞α-SMA和TGF-β1的表达,降低24h尿蛋白、血尿素氮和血肌酐,可能是防治肾小球硬化的部分作用机制。Objective To study the effect of Shenshuning mixture on phenotypic modulation of mesangial cell in glomerulosclerosis rats and its mechanism. Methods Bats models were induced and established by unilateral nephrectomy（Nx） and injection. Bats model of glomerulosclerosis was established by unilateral nephrectomy and intravenous injection of 0.2% Doxorubicin（5 mg/kg）, rats were administered Shenshuning mixture 43.93 g/（ kg · d）, benazepril 10 rag/（ kg · d）, or distilled water respectively. Other 8 sham-operated rats as comparison. 8 weeks later, The expression of glomerular α-SMA and TGF-β1 were studied by immunohistechemical staining, and the ratio of positive area/total glomerttlar capillary area（ SMA/GT and TGF/GT） were analyzed with image analysis software, the changes of weight, 24 h proteinuria, plasma albumin, total serum proteim and blood urine nitrogen, creatinine clearance rate were examined in each group. Results Immunohistechemical staining of glomemli showed that expression of α-SMA and TGF-β1 in Shenshuning treated group and Benazepril treated group were significantly less than those of model group（P 〈0.01 ） and improved rats weights, attenuated 24 h urine protein, blood urine nitrogen and serum creatinine（P 〈0.01 ）. The relatively analysis showed significant corelation of α-SMA and TGF-β1 factors （r = 0. 637, P 〈 0.01 ）. Conclusion Shenshuning mixture can improve glomemlosclerosis by inhibiting phenotypic modulation of mesangial cells and TGF-β1 expression, attenuate 24 h proteinuria excretion, blood urea nitrogen and creatinine.

关 键 词：肾疏宁 肾小球硬化 表型转化 Α-平滑肌肌动蛋白 转化生长因子-Β1 

分 类 号：R259.871[医药卫生—中西医结合]