二至丸与失笑散对胆汁淤积性肝纤维化大鼠uPA的调控.docVIP

　　二至丸与失笑散对胆汁淤积性肝纤维化大鼠uPA的调控 作者：陈珺明　安德明　柳涛　郑培永　邢练军　季光 【摘要】 目的研究不同治则中药复方二至丸与失笑散对胆汁淤积性肝纤维化大鼠uPA/PAI-1纤溶途经的调控作用。方法SD雄性大鼠60只随机分为假手术组和造模组, 造模组于1周后随机分为模型对照组、二至丸组、失笑散组及合方组。各 治疗 组分别给予相应药物灌胃,模型对照组和假手术组给予等量生理盐水灌胃,4周末处死大鼠。观察内容包括一般情况、肝功能、肝组织病理、ethodsSixty male Sprague-Daly divided into 2 groups: Sham operation group and model group. Bile duct ligation method ake the model of cholestasis-induced liver fibrosis. One odel group rats ly divided into four groups :Untreated group , Erzhiedicine intervention group edicine by intragastric administration. Sham operation group and untreated group chloride pled. General state of health , hepatic function (alanine aminotransferase(ALT), aspartate aminotransferase(AST),alkaline phosphatase(ALP), total bilirubin(TBil), and pathological histology of hepatic tissue easured. uPA erase chain raction (RT-PCR) and PAI-1 ALP , ALT and AST levels in three Chinese medicine plex prescription group rats and the serum level of TBil in Shixiaosan and ECS group rats odel group (Plt;0.01).ECS ple recipe in ALP and ALT. All of three plex prescriptions could inhibit liver fibrosis to some extent (Plt;0.01) , but ECS ore obviously than simple recipe.PAI-1mRNA expression edicine plex prescription groups as pared to model group(Plt;0.01),ECS group dEicine plex prescriptions ( Erzhiprove the Hepatic function of cholestasis-induced liver fibrosis rats, alleviate hepatic fibrosis,and ECS is better than simple recipe. The mechanism may be related to regulating the uPA/ PAI-1 fibrinolytic system. 　　Key atrix ,ECM)合成增多而降解相对减少，使过多的ECM 沉积于肝内。肝星状细胞(hepar stellate cell, HSC)是调控肝脏ECM 沉积的最重要细胞，其激活是肝纤维化发生的中心环节。HSC对ECM 调节的重要途径之一就是通过尿激酶型纤溶酶原激活物(uPA)和其抑制物(PAI)的差异表达，调控纤溶酶和基质金属蛋白酶(matrix metalloprotEInase, MMP)家族的活性，以维持ECM 合成与降解之间的平衡。祖国医学普遍认为, “正虚血淤”是肝纤维化的基本病机［1］。本研究旨在观察补益肝肾和活血化淤的经典名方二至丸和失笑散及其合方对大鼠胆汁淤积性肝纤维化形成的影响及其对uPA/PAI的调控作用,为中医药防治以细胞外基质沉积为特征的肝纤维化提供更广阔的途径。 　 　1 材料与仪器 　　1.1 动物 　　SD雄性大鼠60 只, SPF 级,体重(260±20) g,购自上海斯莱克实验动物有限责任公司,许可证号: SCXK (沪) 2003 - 0003。饲养于上海中医药大学附属龙华 医院 实