人参皂苷Rg_1对转化生长因子-β_1诱导的肾小管上皮细胞转分化的影响  

Ginsenoside Rg1 inhibit transdifferentiation in rat renal tubular epethelial cells induced by TGF-β1

作　　者：谢席胜[1] 刘衡川[2] 李会娟[1] 樊均明[3] 

机构地区：[1]四川大学华西医院肾脏科,四川成都610041 [2]四川大学华西公共卫生学院医学检验教研室,四川成都610041 [3]四川大学华西医院人类疾病生物治疗国家重点实验室,四川成都610041

出　　处：《中国中药杂志》2008年第17期2136-2141,共6页China Journal of Chinese Materia Medica

摘　　要：目的:探讨人参皂苷Rg1(Rg1)对转化生长因子-β1(TGF-β1)诱导的肾小管上皮细胞转分化(TEMT)的作用及对细胞外基质(ECM)的影响。方法:将体外培养的正常大鼠肾小管上皮细胞(NRK52E)分为空白对照组,10 mg.L-1TGF-β1刺激组及不同剂量的Rg1干预组(10,20,40 mg.L-1)。应用形态学、免疫组化技术、酶联免疫吸附法、荧光定量PCR,Western蛋白印迹等观察Rg1对TGF-β1诱导的NRK52E细胞转分化的作用及对ECM主要成分胶原Ⅰ(Col-Ⅰ)和纤维粘连蛋白(FN)的影响。结果:与空白对照组相比,NRK52E培养3 d后,TGF-β1刺激组细胞形态学发生明显改变。免疫组织化学和Western蛋白印迹结果显示α-SMA的表达显著增加而E-cadherin的表达明显减少(P<0.05);RT-PCR结果示α-SMA,Col-Ⅰ和FN的mRNA表达明显增高(P<0.05);细胞培养上清液Col-Ⅰ和FN的含量也显著增加(P<0.05);与TGF-β1刺激组相比,各Rg1干预组均不同程度的改善了TGF-β1刺激的细胞形态学改变;有效抑制了α-SMA的表达,部分恢复了E-cadherin的下调(P<0.05);Col-Ⅰ和FN的含量亦明显减少(P<0.05)。结论:TGF-β1可以诱导大鼠TEMT,刺激ECM成分Col-Ⅰ和FN的升高。Rg1呈剂量依赖性地明显地抑制TGF-β1刺激的NRK52E细胞的转分化和ECM的增加。Objective： To investigate the effects of ginsenoside Rg1 on the transdifferentiation of rat renal tubular epethelial cells induced by transforming growth factor-β1 （TGF-β1 ） . Method： Cultured normal rat renal tubular epethelial cells （NRK-52E） were divided into control group, TGF-β1-indueed group and treated with ginsenoside Rg1 at different concentration （10, 20, 40 mg· L^-1 ） group. The morphology of tubular epithelial-myofibmblast transdifferentiation induced by TGF-β1 was observed through light microscope, α-SMA and E-cadherin protein expression were assessed by immunohistochemistry and western blot analyses, α-SMA, collagen Ⅰ and and fibronectin gene expression were assessed by real-time quantitative chain reaction. Enzyme-linked immunosorbent assay was used to quantitatively detect collagen Ⅰ and fibronectin in the supernatant. Result： 10 mg· L^-1 TGF-β1 could induce the transdifferentiation of tubular epithelial myofibroblast, showing fibroblast-like in morphology, with significantly enhanced expression of α-SMA,depressed expression of E-cadherin and increased secretion of fibronectin and collagen Ⅰ （P 〈 0. 05 ） . Compared to TGF-β1-induced group, ginsenoside Rg1 partly abrogated the α-SMA expression and E-cadherin depression triggered by TGF-β1 in tubular epithelial cells in a dose-dependent manner （ P 〈 0. 05 ） . Meanhile, ginsenoside Rg1 blocked morphologic transformation of tubular epithelial cells and decreased levels of collagen Ⅰ and fibronectin （P 〈 0. 05 ） . Conclusion： Ginsenoside Rg1 could inhibit TGF-β1 induced the tubular epithelial-myofibroblast transdifferentiation and decreased levels of collagen Ⅰ and fibronectin in NRK52E.

关 键 词：人参皂苷RG1 转分化 肌成纤维细胞 转化生长因子-β1 细胞外基质 

分 类 号：R285.5[医药卫生—中药学]