鲤鱼汤对阿霉素肾病大鼠肾组织TGF-β1及下游因子表达的影响

Influence of Cyprinus Carpio Decoction on Expression of TGF-β1 and Its Downstream Factors of Adriamycin Nephropathy Rats

本研究探讨鲤鱼汤利尿消肿拮抗肾纤维化保护肾脏的分子机制。阿霉素6.2 mg/kg尾静脉单次注射制备ADRN模型,2 W后干预连续7 W。检测尿、血生化指标,光镜电镜观察肾组织形态变化,免疫组化检测转化生长因子β1(TGF-β1)及下游因子表达。结果发现模型组较对照组12 h尿量(12 h-Uv)减少,血白蛋白(Alb)降低,肾小球硬化指数(GSI)及间质损伤指数(TII)升高,肾组织Smad7表达下调,转化生TGF-β1、成纤维细胞特异性蛋白-1(FSP-1)、I型胶原(Col-I)表达上调;鲤鱼汤组较模型组12 h-Uv增加,血Alb升高,GSI及TII下降,肾组织Smad7表达上调,TGF-β1、FSP-1、Col-Ⅰ表达下调。表明鲤鱼汤的肾保护作用至少部分与其利尿消肿、调节TGF-β1/Smad7信号通路、抑制上皮细胞转分化(EMT)及细胞外基质沉积(ECM)有关。

In this study the underlying molecular mechanism of the protective effect of Cypriuns Carpio Decoction（CCD）on kidney was investigated.ADRN rat model was established by single caudal vein injection of 6.2 mg/kg Adriamycin（ADR）.After ADR injection 2 W,intervention was given for 7 W.Urine and blood samples were taken for biochemical analysis and the kidney was processed for morphological studies.Immunohistochemistry was used to detect protein expression of transforming growth factor β1（TGF-β1）and its related downstream factors including Smad7,collagen I（Col-I）and fibroblast-specific protein 1（FSP1）.Compared with control group,the 12 h urine volume（12 h-Uv）,serum albumin（Alb）and the expression of Smad7 were significantly decreased while glomerulosclerosis index（GSI）,interstitial injury index（TII）,the expression of transforming growth factor-β1（TGF-β1）,fibroblast-specific protein 1（FSP1）and collagen I（Col-I）were significantly increased（P 0.05）in ADRN model group.Compared with ADRN model group,12 h-Uv,Alb and the expression of Smad7 were significantly up-regulated while GSI,TII,the expression of TGF-β1,FSP1 and Col-I were significantly down-regulated（P 0.05）.CCD had some renal protective effect on ADRN partly through inducing diuresis to reduce edema,regulating TGF-β1/Smad7 signaling pathway followed by inhibiting epithelial to mesenchymal transition（EMT）and alleviating the extracellular matrix（ECM）deposition.