尿激酶型纤溶酶原激活物途径在大鼠酒精性肝纤维化形成中的作用  

The role of urokinase-type plasminogen activator and type-1 plasminogen activator inhibitor fibrinolytic system in the development of alcoholic liver fibrosis in rats

作　　者：陈珺明[1] 田淑霞[1] 王磊[2] 邢练军[2] 郑培永[2] 季光[2] 

机构地区：[1]上海交通大学附属第六人民医院中医科,200233 [2]上海中医药大学龙华医院消化内科上海中医药大学脾胃病研究所

出　　处：《肝脏》2011年第6期461-466,共6页Chinese Hepatology

基　　金：教育部新世纪优秀人才支持计划资助项目(NCET07-0563);上海教委重点学科资助项目(J50305);上海市卫生局科技基金资助项目(2010L060A)

摘　　要：目的通过观察尿激酶型纤溶酶原激活物(uPA)及其抑制物(PAI-1)在大鼠酒精性肝纤维化形成中的动态变化,探讨uPA纤溶途径在酒精性肝纤维化形成中的作用。方法雄性SD大鼠随机分为空白组、四氯化碳(CCl_4)组和造模组。采用56度二锅头酒、玉米油、吡唑混合物灌胃联合腹腔注射CCl_4橄榄油溶液(CCl_4:橄榄油=1:3)的方法建立酒精性肝纤维模型。分别于4、8、10、12周处死大鼠,观察大鼠肝功能及肝组织病理学改变;采用蛋白印迹法、荧光定量PCR、免疫荧光法检测uPA和PAI-1蛋白及mRNA表达动态变化。结果与空白组比较,CCl_4组无显著差异;模型组肝纤维化程度明显加重(P<0.01),血清ALT、AST水平明显升高(P<0.05);uPA及PAI-1水平明显升高,且PAI-1升高幅度大于uPA(P<0.01)。结论 uPA纤溶途径在酒精性肝纤维化中具有重要作用,随着酒精性肝纤维化的形成,uPA、PAI-1均明显升高,但以PAI-1升高幅度更大。Objective To study the role of urokinase-type plasminogen activator and type-1 plasminogen activator inhibitor fibrinolytic system in alcoholic liver fibrosis in rats by observing the dynamically variety of them in the development of alcoholic liver fibrosis.Methods SD rats were divided into three groups randomly：control group,CCl_4 group and experiment group.The experiment group was ingested the mixture（560 mL/L alcohol,10 mL/kg per day; corn oil 2 mL/kg per day;pyrazole 25 mg/kg per day） once a day and peritoneal injection 0.3 mL/kg 25%solution of CCl_4 in olive oil twice a week.The CC1_4 group received peritoneal injection as the experiment group and ingested saline （12 mL/kg per day）.Control group received peritoneal injection and ingested saline with the equal volume as the experiment group.The rats were anaesthetized and killed at the 4,8,10 and 12 weeks,The levels of ALT,AST in the serum were analyzed.Pathological changes in liver tissues were observed.The expression of uPA and PAI-1 were evaluated with Western blot,Immuno fluorescence,Real-time PCR.Results No significant difference was found between CCL group and control group.Compared with control group,the severity of liver fibrosis in the model group increased（P0.01）,and serum ALT,and AST levels increased as well,especially the AST（P0.05）;Also uPA and PAI-1 levels were significantly elevated,and PAI-1 increased more signficantly than uPA（P0.01）.Conclusion uPA fibrinolysis system plays a key role in the development of alcoholic liver fibrosis,As for the formation of alcoholic liver fibrosis,the amount of uPA and PAI-1 significantly increased,but PAI-1 increased much more obviously.

关 键 词：酒精性肝纤维化 尿激酶型纤溶酶原激活物 Ⅰ型纤溶酶原激活物抑制剂 

分 类 号：R575.2[医药卫生—消化系统]