川芎嗪对土三七诱导的肝小静脉闭塞病小鼠肝组织PAI-1表达的影响

Effect of Ligustrazine on Expression of Plasminogen Activator Inhibitor-1 in Mice with Gynura Segetum Induced Hepatic Veno-occlusive Disease

目的探讨川芎嗪对土三七诱导的肝小静脉闭塞病(HVOD)小鼠肝组织中纤溶酶原激活物抑制剂1(PAI-1)表达的影响。方法 115只昆明小鼠随机分为土三七组(A组,30只)、低剂量川芎嗪干预组(B组,30只)、高剂量川芎嗪干预组(C组,30只)和正常对照组(D组,25只)。A组给予土三七浓缩煎液灌胃(30 g.kg-1.d-1),B组给予土三七浓缩煎液(30 g.kg-1.d-1)+川芎嗪(100 mg.kg-.1d-1)灌胃,C组给予土三七浓缩煎液(30 g.kg-.1d-1)+川芎嗪(200 mg.kg-1.d-1)灌胃,D组给予PBS(30 mL.kg-1.d-1)灌胃,30 d后处死小鼠。留取肝组织行HE和Masson染色并检测血清中ALT、AST、ALB、TBIL、DBIL的水平。采用免疫组化法检测肝组织中PAI-1蛋白的表达。结果 A组有24只小鼠成模,其肝功能(ALT、AST、TBIL、DBIL、ALB)较D组有明显异常(P<0.05),PAI-1蛋白表达水平显著高于D组(P<0.05);不同剂量川芎嗪干预组小鼠肝功能(ALT、AST、TBIL、DBIL、ALB)较A组均有所改善,其差异有统计学意义(P<0.05),PAI-1蛋白表达水平显著低于A组(P<0.05),其中C组改善较为明显(P<0.05)。结论川芎嗪干预能有效防治HVOD,以高剂量(200 mg.kg-.1d-1)疗效更为确切。其可能的机制是通过下调PAI-1表达,阻止凝血系统活化,从而有效防治HVOD。

Objective To investigate the effect of ligustrazine on plasminogen activator inhibitor-1 （PAI-1） expression in mice with gynura segetum induced hepatic veno-occlusive disease. Methods A total of 115 female Kunming （KM） mice were randomly divided into 4 groups,and respectively gavaged with gynum segetum （group A）,gynura segeturo ＋ low dose hgustrazine （group B ）,gynura segetum ＋ high dose hgustrazine （group C ） and PBS （group D）. All the mice were sacrificed 30 days later. Blood and hver samples were collected. Weight of mice, weight ratio of liver to body, serum biochemistry parameters （including ALT, AST, TBIL, DBIL and ALB） were measured. Liver sec- tions were evaluated by hght microscopy with modified scoring system. Immunohistochemistry was used to detect the expression of PAI-1 protein. Results Totally 24 mice in group A developed HVOD, which showed increased liver ratio, TBIL, DBIL, ALT, AST and decreased ALB compared with group D （P 〈 0.05）. The clinical syroptoms and biochemistry parameters were improved after different doses of ligns- trazine administration（P 〈 0.05 ）,the changes were more significant in group C. Compared with group D,the expression of PAI-1 significantly increased in group A（P 〈 0.05）and slightly increased in group B and C（P〉 0.05）. Conclusion Lignstrazine has good therapeutic effect on HVOD,which significantly improved clinical manifestations and liver function. High dose of lignstrazine （200 mg .kg^-1 .d^-1）may be a preferable dose. One of the possible mechanisms may be the reduction of PAI-1 expression by ligustrazine.