高山红景天对肝纤维化大鼠Smad3mRNA表达的影响

摘要

Objective At home and abroad, there lacks ideal antifibrotic drugs, for the scientific development of traditional Chinese medicine into new, effective and safe anti-hepatic fibrosis drugs, Rhodiola sachaliensis A. Bor is investigated here for its therapeutic effects on experimental hepatic fibrosis in rats and its mechanism. Methods Hepatic fibrosis rat models were established with the treatment of carbon tetrachloride ( CC14 ) for eight weeks. All the experimental rats were divided into five groups : normal group (no treatment) , model group (CCl4only) and 3 test groups ( CC14 and colchicines or high or low dosage of Rhdiola sa-chaliensis A. Bor). Serum levels of hyaluronic acid (HA), laminin (LN), pro-collagen type IE peptide (PCI) and collagen type IV peptide (CIV ) were detected by radio immunoassay. The Smad^mRNA expression in rat hepatic tissues were examined by using a RT-PCR technology. The liver histopathological changes were observed with HE or special collegin fibrosis staining and the liver ul-trasructures were observed under an electromicroscope. Results Comparing with the model group, Rhodiola sachaliensis A. Bor treatments significantly decreased the serum levels of LN, PC IE , HA and CIV ( P < 0. 01 ) ; markedly decreased the expression ofrnSmad3mRNA in the rat hepatic tissues (P<0. 01); and obviously improved the liver histopathological changes . Conclusion High dosage of Rhodiola sachaliensis A. Bor can effectively suppress the de -velopment of hepatic fibrosis , this possibly is achieved by down regulating the Smad3 mRNA expression in hepatic tissues and reducing the secretion of extracellular matrix.%目的 目前国内外尚缺乏理想的抗肝纤维化药物.为科学研制新型、高效、安全的抗肝纤维化药物,观察单方生药高山红景天对实验性肝纤维化大鼠的治疗效果,并探讨其作用机制.方法 用四氯化碳诱导大鼠肝纤维化模型,将实验动物随机分为正常对照组、模型组、秋水仙碱组、红景天高剂量组、红景天低剂量组.除正常对照组外,其余4组均用四氯化碳诱发肝纤维化.各组于造模第8周末处死动物,分别用放射免疫法检测血清层黏连蛋白(laminin,LN),Ⅲ型前胶原(pro-collagen type Ⅲ,PCⅢ),透明质酸(hyaluronic acid,HA)及Ⅳ型胶原(collagen type Ⅳ peptide,CⅣ);RT-PCR检测肝组织Smad3mRNA的表达;作HE染色和胶原纤维特殊染色行肝组织病理形态学观察及电镜观察各组大鼠肝超微结构.结果 与模型组大鼠比较,经该中药治疗,大鼠血清中LN、PCⅢ、HA、CⅣ水平明显降低(P＜0.01);大鼠肝组织内Smad3mRNA表达明显下降(P＜0.01);病理学检测大鼠肝组织病理学检测红景天高剂量组改善显著.结论 高山红景天高剂量组能有效地抑制肝纤维化的发展,可能是通过下调肝组织内Smad3mRNA表达,降低肝细胞外基质(extracellular matrix,ECM)的分泌而达到的.