Shi Shao-Hua, Zheng Shu-Sen, Jia Chang-Ku, Zhu You-Fa, Xie Hai-Yang
Department of Hepatobiliary Surgery, the First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China.
Acta Pharmacol Sin. 2004 Jan;25(1):98-103.
To investigate the inhibitory effect of tea polyphenols (TP) on the transforming growth factor-beta1 (TGF-beta1) expression in rat model of cyclosporine A (CsA)-induced chronic nephrotoxicity.
The rat model of CsA-induced chronic nephrotoxicity was used, 4 groups of rats were respectively treated with vehicle (0.1 mL/kg/d sc), TP (80 mg/kg/d ig), CsA (15 mg/kg/d sc) and TP plus CsA (CsA 15 mg/kg/d sc+TP 80 mg/kg/d, ig). At the end of day 28 of treatment, serum and urine are analyzed for creatinine clearance, kidney tissue for pathologic analysis. The TGF-beta1 mRNA and its protein expression were detected by RT-PCR, immunohistochemistry, and Western blot.
CsA-treated rats had increased renal expression of TGF-beta1 mRNA and its protein, compared with the vehicle- or TP-treated controls. The renal function and interstitial fibrosis were ameliorated and renal expression of TGF-beta1 mRNA and its protein was decreased in animals treated with CsA plus TP, compared with animals treated with CsA alone (P<0.05).
TP significantly inhibits renal expression of TGF-beta1 in rat model of cyclosporine-induced chronic nephrotoxicity, suggesting that the decreased renal expression of TGF-beta1 exerted by TP is one of mechanisms to protect renal function and tissue structure.
研究茶多酚(TP)对环孢素A(CsA)诱导的大鼠慢性肾毒性模型中转化生长因子-β1(TGF-β1)表达的抑制作用。
采用CsA诱导的大鼠慢性肾毒性模型,4组大鼠分别给予溶媒(0.1 mL/kg/d皮下注射)、TP(80 mg/kg/d灌胃)、CsA(15 mg/kg/d皮下注射)以及TP加CsA(CsA 15 mg/kg/d皮下注射+TP 80 mg/kg/d灌胃)处理。在治疗第28天结束时,分析血清和尿液中的肌酐清除率,对肾组织进行病理分析。通过逆转录聚合酶链反应(RT-PCR)、免疫组织化学和蛋白质印迹法检测TGF-β1 mRNA及其蛋白表达。
与溶媒或TP处理的对照组相比,CsA处理的大鼠肾组织中TGF-β1 mRNA及其蛋白表达增加。与单独给予CsA的动物相比,CsA加TP处理的动物肾功能和间质纤维化得到改善,肾组织中TGF-β1 mRNA及其蛋白表达降低(P<0.05)。
在CsA诱导的大鼠慢性肾毒性模型中,TP显著抑制肾组织中TGF-β1的表达,提示TP降低肾组织中TGF-β1的表达是其保护肾功能和组织结构的机制之一。