荔枝核总黄酮对大鼠肝纤维化Smad3、Smad4及TIMP-1信号表达的影响  

Effect of total flavone from Litchi chinensis Sonn on Smad3, Smad4 and TIMP-1 expression in a rat model of liver fibrosis

作　　者：黄红[1] 康毅[1] 黄旭平[1] 王晨晓[1] 罗伟生[1] 

机构地区：[1]广西中医药大学,广西壮族自治区南宁市530299

出　　处：《世界华人消化杂志》2016年第2期176-186,共11页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81360530~~

摘　　要：目的:观察荔枝核总黄酮(total flavone from Litchi chinensis Sonn,TFL)对二甲基亚硝胺(dimethylnitrosamine,DMN)诱导的肝纤维化大鼠肝脏组Smads信号通路中关键信号传导分子Smad3、Smad4及基质金属蛋白酶抑制剂-1(tissue inhibitor of metalloproteinase-1TIMP-1)表达水平的变化,探讨TFL抗肝纤维化的作用机制.方法:90只S D大鼠随机平均分成正常对照组、模型组、秋水仙碱组不同浓度的TFL[200、100、50 mg/(kg·d)].用DMN腹腔注射诱导大鼠肝纤维化模型,造模同时灌胃给药.1次/d,共给6 wk,于实验第6周后处死大鼠,取血清测定谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate transaminase,AST)的含量.取留取肝脏同一部位行Masson染色观察大鼠病理改变及肝纤维化程度;免疫组织化学法检测Smad3、Smad4、TIMP-1表达量,实时荧光定量PCR检测(real-time quantitative PCR,qRT-PCR)检测Smad3、Smad4、TIMP-1m RNA表达量.结果:与模型组比较,TFL能降低血清ALT、AST含量,Masson染色病理显示TFL能显著减轻大鼠肝纤维化程度;与空白对照组比较,模型组大鼠的肝纤维化程度明显增加,肝组织Smad3、Smad4及TIMP-1的表达明显增强(P<0.05);与模型组比较,TFL各剂量组和秋水仙碱组肝组织Smad3、Smad4、TIMP-1的表达不同程度的降低(P<0.05).结论:T F L可减轻实验性大鼠肝损伤及改善肝纤维化程度,其机制与降低S m a d3、Smad4及TIMP-1的表达有密切关系,可能与改善肝功能、抑制肝细胞变性坏死,从而抑制胶原蛋白的合成和沉积减少细胞外基质有关.AIM： To observe the effect of total flavone from Litchi chinensis Sonn （TFL） on dimethyl- nitrosamine （DMN） induced hepatic fibrosis and the expression of Smad3, Smad4 and TIMP-1 in rat liver tissue, to explore the antifibrotic mechanism of TFL. METHODS： Ninety male SD rats were randomly divided into a normal control group, a fibrosis model group, a colchicine positive control group, and high-, medium-, and low-dose TFL groups [200, 100, and 50 mg/（kg＇d）, respectively]. Liver fibrosis was induced in rats by intraperitoneal injection of 0.5% DMN solution. Colchicine or TFL was given during modelling by garage, once a day, for 6 wk. Rats were killed after 6 wk, and the levels of alanine aminotransferase （ALT） and aspartate transaminase （AST） were tested using an automatic biochemical analyzer. Liver tissue samples were taken for Masson staining to observe the pathological changes and the degree of liver fibrosis in rats. The protein and mRNA expression of Smad3, Smad4, and TIMP-1 was detected by immunohistochemistry and real-time quantitative PCR （RT-PCR）, respectively. RESULTS： Compared with the model group, the levels of ALT and AST were significantly decreased in the TFL groups. Compared with the normal control group, the extent of fibrosisin the model group increased significantly, and the expression of Smad3, Smad4 and TIMP-1 in liver tissue was significantly enhanced （P 〈 0.05）. Compared with the model group, the expression of Smad3, Smad4 and TIMP-1 showed varying degrees of down-regulation in the TFL groups and colchicine groups. TFL can reduce liver injury and improve liver fibrosis in rats with liver fibrosis, and the underlying mechanism may be closely related with decreasing the expression of Smad3, Smad4 and TIMP-1.

关 键 词：肝纤维化 荔枝核总黄酮 SMAD3 SMAD4 TIMP-1 

分 类 号：R285.5[医药卫生—中药学]