【摘要】 目的探讨蝙蝠葛碱（DAU）对CCl₄诱导小鼠肝纤维化（LF）的影响和机制。方法 C57BL/6小鼠随机分成对照组、模型组、秋水仙碱组(秋水仙碱1mg·kg^-1)、DAU高、中、低剂量组(40,20,10mg·kg^-1)。采用30%CCl₄(1μl·g^-1)腹腔注射诱导LF小鼠模型。放射免疫法检测血清透明质酸（HA）、层粘连蛋白（LN）、III型前胶原（PCIII）和IV型胶原（CIV）水平。生化分析法检测血清谷丙转氨酶（ALT）、谷草转氨酶（AST）水平。酶联免疫法检测肝脏转化生长因子-β1（TGF-β1）和肿瘤坏死因子-α（TNF-α）水平。电子显微镜观察小鼠肝组织形态结构并计算肝脏器指数。结果与模型组比较,DAU高、中剂量组小鼠血清HA、LN、PC-III、CIV、ALT和AST明显降低（P<0.05）,TGF-β1和TNF-α水平明显降低（P<0.05）,小鼠肝脏病理纤维化明显减轻,肝脏器指数明显降低（P<0.05）。结论 DAU能有效减轻CCl₄诱导LF小鼠肝脏损伤,降低LF程度,其机制与抑制肝脏TGF-β1和TNF-α表达有关。更多还原

【Abstract】 Objective To investigate the protective effects of Dauricine（ DAU） against liver fibrosis induced by CCl₄ in mice and their mechanism. Methods C57 BL /6 mice were randomly divided into control group,model group,colchicine group( colchicine1mg·kg^-1),DAU high- dose group( 40mg·kg^-1),DAU medial- dose group( 20mg·kg^-1),DAU low- dose group( 10mg·kg^-1). By using intraperitoneal injection of 30% CCl₄( 1μl·g^-1) induce liver fibrosis model mice. The radioimmunoassay was used to determine hyaluronic acid（ HA）,laminin（ LN）,procollagen III（ PCIII） and IV collagen（ CIV） levels in serum. The biochemical analysis was used to determine alanine aminotransferase（ ALT）,aspartate aminotransferase（ AST）. The enzyme-linked immuno sorbent assay（ ELISA） was applied for detecting transforming growth factor- β1（ TGF- β1） and tumor necrosis factor- α（ TNF- α） levels in the liver. After the treatment all animals were sacrificed,morphology of liver tissue was observed by optical electron microscopy,calculated the organ coefficients of hepatic. Results Compared with the model group,DAU high-dose group and DAU medial- dose group HA,LN,PC- III,CIV,ALT and AST in serum of mice significantly decreased（ P <0. 05）; TGF- β1 and TNF- α in the liver significantly decreased（ P < 0. 05）; the liver pathological variations of fibrotic mice obviously; organ coefficients of hepatic significantly decreased（ P < 0. 05）. Conclusion DAU could attenuate the CCl₄- induced immunological liver injury and the fibrosis level in mice. The mechanisms possibly contribute to down- regulating expression of TGF- β1 and TNF- α protein in liver of mice.更多还原