补肾柔肝方对二甲基亚硝胺诱导大鼠肝纤维化的预防作用及其机制研究

Bushen Rougan Recipe in prevention of hepatic fibrosis in rats induced by dimethylnitrosamine:a study on its preliminary mechanism

目的:探讨补肾柔肝方对二甲基亚硝胺(dimethylnitrosamine,DMN)诱导大鼠肝纤维化的预防作用及初步机制。方法:雄性Wistar大鼠40只,随机分为正常对照组(n=10)、模型组(n=15)及补肾柔肝方预防组(n=15)。模型组和补肾柔肝方预防组以10mg/kg DMN腹腔注射,1次/d,每周连续3d,共4周。模型组在造模同时给予生理盐水灌胃,补肾柔肝方预防组在造模同时给予补肾柔肝方灌胃,共4周;第4周末处死全部大鼠,留取血清及肝组织标本。采用全自动生化分析仪检测血清总胆红素(total bilirubin,Tbil)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、白蛋白等;应用逆转录聚合酶链式反应法检测肝组织结缔组织生长因子(connective tissue growth factor,CTGF)和Ⅰ型胶原mRNA的表达。结果:补肾柔肝方预防组大鼠一般状态明显好于模型组;模型组大鼠死亡率为13.33%(2/15),补肾柔肝方预防组死亡率为6.67%(1/15);模型组大鼠腹水发生率为46.67%(7/15),补肾柔肝方预防组大鼠腹水发生率为20%(3/15),两组比较差异有统计学意义(P<0.01);补肾柔肝方组肝功能较模型组有显著改善(P<0.01)。模型组肝组织CTGF和Ⅰ型胶原mRNA表达明显增强,补肾柔肝方预防组与模型组相比明显减弱(P<0.01)。结论:补肾柔肝方可通过抑制大鼠肝组织CTGF和Ⅰ型胶原mRNA的表达,达到抗肝纤维化的作用。

Objective： To study the effects of Bushen Rougan Recipe （BSRGR）, a compound medicine, on hepatic fibrosis in rats induced by dimethylnitrosamine （DMN）, and mechanism. Methods： A total of 40 male Wistar rats were randomly divided into normal control group （n=15）, andBSRGR group （n=15）. Except for the rats in normal control traditional Chinese herbal to explore its preliminary group （n= 10）, untreated group, hepatic fibrosis in rats was induced by peritoneal injection of DMN for 4 weeks. And the rats in the BSRGR group were also intragastrically administered BSRGR within the 4-week course. At the end of the 4-week course, rats were all sacrificed. The liver functions were determined by automatic biochemistry analyzer, including serum total bilirubin （Tbil）, alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, and albumin. Expressions of connective tissue growth factor （CTGF） and collagen type 1 mRNA in liver tissue were detected by reverse transcription polymerase chain reaction. Results： It was found that the serum Tbil level and the activities of AST, ALT were declined in the BSRGR group as compared with those in the untreated group （P〈0.0]）. The serum albumin content in the BSRGR group was increased as compared with that in the untreated group （ P 〈0.01）. The expressions of collagen type Ⅰ andCTGF mRNAsin the untreated group were higher than those in the BSRGR group （P〈0.0]）. Conclusion： BSRGR can decrease the expressions of collagen type Ⅰ and CTGF mRNAs in the rats with hepatic fibrosis, which may be one of possible mechanisms in treating hepatic fibrosis.