扶正化瘀方对非酒精性脂肪性肝纤维化及uPA/PAI-1的作用及机制  

Effects of Fuzheng Huayu recipe on hepatic expression of uPA/PAI-1 in mice with non-alcoholic fibrosing steatohepatitis

作　　者：南月敏[1] 米红梅[1] 王荣琦[1] 孔令波[1] 张玉果[1] 任伟光[1] 李会[1] 

机构地区：[1]河北医科大学第三医院中西医结合肝病科,石家庄050051

出　　处：《肝脏》2012年第11期771-774,共4页Chinese Hepatology

基　　金：Pearl Ocean Liver Fibrosis Grant(001)

摘　　要：目的探明非酒精性脂肪性肝纤维化进展中扶正化瘀方对小鼠肝组织uPA/PAI-1表达的影响及作用机制。方法选用7～8周龄健康雄性C57BL/6J小鼠,蛋氨酸-胆碱缺乏(methionine and choline deficient,MCD)饮食喂养8周,建立非酒精性脂肪性肝纤维化模型,采用扶正化瘀方进行干预实验,蛋氨酸-胆碱充足饮食设立对照组。HE、Masson染色观察肝脂肪变、炎性反应及纤维化程度;RT-PCR和Western印迹检测肝组织纤溶酶原激活物抑制因子-1(plasminogen activator inhibitor-1,PAI-1)、尿激酶型纤溶酶原激活物(urokinase type plasminogen activator,uPA)、转化生长因子β1(transforming growth factor beta1,TGF-β1)mRNA及蛋白的表达。多组间比较采用单因素方差分析,组间比较采用Student-Newman-Keuls法。结果模型组小鼠肝组织呈现大泡性肝细胞脂肪变,伴肝细胞气球样变、小叶内点/灶状坏死及炎性细胞浸润、可见窦周纤维化及纤维间隔形成,肝组织PAI-1、uPA、TGF-β1mRNA及蛋白表达水平较对照组显著升高;应用扶正化瘀方组小鼠肝脂肪变、炎性反应及纤维化程度较模型组明显减轻,PAI-1、TGF-β1mRNA及蛋白表达显著减少(P<0.05),而uPA表达显著增多(P<0.05)。对照组、模型组、扶正化瘀方组上述基因mRNA及蛋白表达水平依次为,PAI-1:0.25±0.02、1.43±0.10、0.84±0.16和0.30±0.08、1.40±0.16、0.90±0.17;uPA:0.42±0.02、1.03±0.13、1.22±0.06和0.34±0.08、1.15±0.07、1.44±0.07;TGF-β1:0.54±0.06、1.17±0.06、1.02±0.07和0.37±0.07、1.43±0.13、0.99±0.13(P<0.05)。结论扶正化瘀方可通过上调uPA、下调PAI-1及TGF-β1表达,阻止小鼠非酒精性脂肪性肝纤维化的发生与发展。Objective To investigate the potential effects and molecular mechanism of Fuzheng Huayu recipe （FZHY） on hepatic expression of uPA/PAI-1 in non-alcoholic fibrosing steatohepatitis. Methods C57BL/6J mice were fed with methionine-choline deficient （MCD） diet for 8 weeks to induce non-alcoholic fibrosing steatohepatitis administrated with FZHY. HE and Masson stains were performed for observation of hepatic steatosis, inflammation and fibrosis in the liver sections. Hepatic mRNA and protein expressions of plasminogen activator inhibitor-1 （PAI-1）, urokinase type plasminogen activator （uPA） and transforming growth factor beta 1 （TGF-β1） were detected by RT-PCR and western blot. Results Mice fed with MCD diet for 8 weeks showed severe hepatic injuries, including steatosis, inflammatory infiltration and fibrosis, which were associated with enhanced hepatic expression of PAI-1, uPA and TGF-β1. FZHY could ameliorate the liver injury by down-regulating PAI-1 and TGF-β1 expressions and up-regulating uPA expression. The mRNA and protein expressions of the related genes in control group, model group and FZHY group were as following, respectively, PAI-I： 0.25±0.02, 1.43±0.10, 0.84±0.16 and 0.30±0.08, 1.40±0.16, 0.90±0. 17; uPA.. 0.42±0.02, 1.03± 0.13, 1.22± 0.06 and 0.34 ± 0.08, 1.15 ± 0. 07, 1.44 ± 0. 07; TGF-131： 0. 54 ± 0. 06, 1.17 ± 0.06, 1.02 ± 0. 07 and 0.37 ± 0. 07, 1.43 4- 0.13, 0.99 ± 0.13 （P〈0. 05）. Conclusion FZHY could ameliorate hepatic inflammatory response andfibrogenesis through enhancing uPA expression, suppressing PAI-1 and TGF-β1 expressions.

关 键 词：非酒精性脂肪性肝纤维化 扶正化瘀方 纤溶酶原激活物抑制剂-1 尿激酶型纤溶酶原激活物 

分 类 号：R285.5[医药卫生—中药学]