通天草提取物对大鼠肝纤维化的影响和机制

Effect of Aqueous extract from Waternut herb on liver fibrosis rats and its mechanism

目的探讨通天草提取物(AEWH)对CCl_4诱导大鼠肝纤维化(LF)的影响和机制。方法 SD大鼠随机分成对照组,模型组,治疗组(秋水仙碱0.001 g/kg),AEWH高、中、低剂量组(AEWH 3、1.5、0.75 g/kg)。采用40%CCl_4(1 ml/kg)腹腔注射诱导LF大鼠模型。放射免疫法检测大鼠血清透明质酸(HA)、层黏连蛋白(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)、总蛋白(TP)和白蛋白(ALB)水平。电子显微镜观察大鼠肝组织镜下形态结构并计算肝脏脏器指数。酶联免疫法检测肝脏中转化生长因子(TGF)-β1和肿瘤坏死因子(TNF)-α水平。结果与模型组比较,AEWH高、中剂量组大鼠血清HA、LN、PCⅢ、CⅣ、ALT和AST明显降低(P<0.05),TP和ALB明显升高(P<0.05),大鼠肝脏病理纤维化明显减轻,肝脏脏器指数明显降低(P<0.05),肝TGF-β1和TNF-α明显降低(P<0.05)。结论 AEWH可减轻CCl4诱导LF大鼠肝脏损伤,降低LF程度。AEWH治疗LF的机制与抑制大鼠肝脏TGF-β1和TNF-α表达有关。

Objective To investigate the protective effects of Aqueous extract from Waternut herb（ AEWH） against liver fibrosis induced by CCl4 in rats and their mechanism. Methods Sprague-Dawley rats were randomly divided into control,model,treatment（ colchicine0. 001 g / kg）,AEWH high-,medial-,low-dose（ AEWH 3,1. 5 and 0. 75 g / kg） groups. Liver fibrosis model rat was induced by intraperitoneal injection of 40% CCl4（ 1 ml/kg）. The radioimmunoassay was used to determine hyaluronic acid（ HA）,laminin（ LN）,procollagen Ⅲ（ PCⅢ） and Ⅳ collagen（ CⅣ） levels in serum of rats. The biochemical analysis was used to determine alanine aminotransferase（ ALT）,aspartate aminotransferase（ AST）,total protein（ TP） and albumin（ ALB） levels in serum of rats. After the treatment all animals were sacrificed,morphology of liver tissue was observed by optical electron microscopy to calculate the organ coefficients of liver. The enzyme-linked immunosorbent assay（ ELISA） was applied for detecting transforming growth factor（ TGF）-β1 and tumor necrosis factor（ TNF）-α levels in the liver. Results Compared with the model group,HA,LN,PC-Ⅲ,CⅣ,ALT and AST in serum of rats were significantly decreased（ P〈0. 05）; TP and ALB in serum of rats were significantly increased（ P〈0. 05）; the liver pathological variations of fibrotic rats were obvious; organ coefficients of liver were significantly decreased（ P〈0. 05）; TGF-β1 and TNF-α in the liver of rats were significantly decreased（ P〈0.05） in AEWH high-dose and medial-dose groups. Conclusions AEWH could attenuate the CCl4-induced immunological liver injury and the fibrosis level in rats. The mechanisms possibly contribute to down-regulation expression of TGF-β1 and TNF-α in liver of rats.