罗格列酮对类胰蛋白酶诱导的大鼠肝星状细胞Ⅰ型胶原及过氧化物酶体增殖物活化受体γ表达的影响  

Effects of rosiglitazone on tryptase-induced type Ⅰ collagen and peroxisome proliferator-activator receptor-γ expression in hepatic stellate cells in rats

作　　者：毕丽青[1] 郝彦琴[1] 王翠玲[1] 赵龙凤[1] 

机构地区：[1]山西医科大学第一医院防保科,太原030001

出　　处：《中国药物与临床》2014年第1期13-15,共3页Chinese Remedies & Clinics

基　　金：山西省科技厅科技攻关项目(201103113012-4);山西省卫生厅科技攻关项目(200809)

摘　　要：目的观察罗格列酮对类胰蛋白酶诱导的大鼠肝星状细胞(HSC)Ⅰ型胶原及过氧化物酶体增殖物活化受体γ(PPARγ)表达的影响,探讨罗格列酮抑制肝纤维化的作用机制。方法将大鼠HSC-T6进行体外培养,取对数生长期细胞分为空白对照组,1、10、100 ng/ml类胰蛋白酶组,10 ng/ml类胰蛋白酶+(5、10、20μmol/L)罗格列酮组。用半定量反转录-聚合酶链反应(RT-PCR)法检测HSCⅠ型胶原及PPARγ的表达。结果类胰蛋白酶可以诱导大鼠HSCⅠ型胶原表达并使HSC PPARγ表达减少(P<0.05),罗格列酮可以不同程度抑制类胰蛋白酶的上述效应,且各组Ⅰ型胶原的表达水平均低于10 ng/ml类胰蛋白酶组(P<0.05),各组PPARγ的表达水平均高于10 ng/ml类胰蛋白酶组(P<0.05),并呈剂量依赖性(P<0.05)。结论罗格列酮能够上调PPARγ表达并抑制类胰蛋白酶诱导的HSCⅠ型胶原的表达,抑制肝纤维化的发生。Objective To investigate the effects of rosiglitazone on tryptase-induced collagen I and peroxi-some proliferator-activated receptor γ （PPARγ） expression in hepatic stellate cells （HSCs） in rats, and to explore the anti-fibrotic mechanisms of rosiglitazone. Methods Rat HSCs （HSC-T6） were subject to incubation in vitro and allo-cated to blank control group, 1, 10, 100 ng/ml tryptase treatment group and 10 ng tryptase plus 5, 10, 20 μg/ml rosiglitazone treatment groups. The expression of collagen Ⅰ and PPARγ mRNAs was assessed by means of semi-quantitative reverse transcriptase polymerase chain reaction. Results Tryptase induced collagen Ⅰ expression yet at-tenuated PPARγ expression of the HSCs （P〈0.05）, which could be mitigated by rosiglitazone administered at various concentrations. The expression of collagen Ⅰ in rosiglitazone treatment group was lower than that in 10 ng tryptase treatment group （P〈0.05）. Compared with 10 ng/ml tryptase treatment group, rosiglitazone at various concentrations dose-dependently yielded an increased expression of PPARγ（P〈0.05）. Conclusion Rosiglitazone inhibits the devel-opment of liver fibrosis by up-regulation of PPARγ expression and attenuation of collagen Ⅰ expression.

关 键 词：肝硬化 胶原Ⅰ型 过氧化物酶体增殖物激活受体 

分 类 号：R965[医药卫生—药理学]