川芎嗪对土三七诱导的小鼠肝小静脉闭塞病治疗机制的研究  

Mechanism of Therapeutic Effect of Ligustrazine on Hepatic Veno-occlusive Disease Induced by Sedum aizoon in Mice

作　　者：陈哲[1] 刘竟芳[1] 朱洪怡[2] 杨丽[3] 霍继荣[2] 

机构地区：[1]长沙市中心医院老年医学科,410004 [2]中南大学湘雅二医院消化内科 [3]湖南省人民医院消化内科

出　　处：《胃肠病学》2016年第1期21-25,共5页Chinese Journal of Gastroenterology

基　　金：湖南省科技厅资助(2009FJ3102)

摘　　要：背景:肝小静脉闭塞病(HVOD)临床上以肝肿大、黄疸、腹水和体重增加为特征,目前尚缺乏有效的治疗手段。本课题前期研究发现川芎嗪对土三七诱导的小鼠HVOD具有治疗作用。目的:探讨川芎嗪对土三七诱导的小鼠HVOD的治疗机制。方法:将115只小鼠随机分为土三七组(土三七浓缩煎液30 g·kg^(^(-1))·d^(-1)灌胃)、低剂量川芎嗪干预组(土三七浓缩煎液30 g·kg^(-1)·d^(-1)+川芎嗪100 mg·kg^(-1)·d^(-1)灌胃)、高剂量川芎嗪干预组(土三七浓缩煎液30 g·kg^(-1)·d^(-1)+川芎嗪200 mg·kg^(-1)·d^(-1)灌胃)和正常对照组(PBS 30 g·kg^(-1)·d^(-1)灌胃),30 d后处死所有小鼠。行HE染色和Masson染色,以RT-PCR法和蛋白质印迹法分别检测肝组织中组织因子(TF)、核因子(NF)-κBp65、早期生长反应因子^(-1)(Egr^(-1))mRNA和蛋白表达。结果:HE染色和Masson染色结果显示川芎嗪可明显改善HVOD小鼠肝组织病理损伤。土三七组TF、NF-κBp65和Egr^(-1) mRNA和蛋白表达显著高于正常对照组,组间差异有统计学意义(P<0.05);川芎嗪干预后,TF、NF-κBp65和Egr^(-1) mRNA和蛋白表达均不同程度下降(P<0.05),以高剂量组下降更为明显,而高剂量川芎嗪干预组与正常对照组相比差异无统计学意义(P>0.05)。结论:川芎嗪可能通过下调NF-κBp65和Egr^(-1)表达降低TF水平,阻止凝血系统活化,从而有效治疗HVOD,且高剂量川芎嗪的疗效更为确切。Background： Hepatic veno-occlusive disease（ HVOD） is a disease characterized by hepatomegaly,jaundice,ascites,weight gain and lack of effective treatment currently. Our prophase research showed that ligustrazine had therapeutic effect on Sedum aizoon induced HVOD in mice. Aims： To investigate the mechanism of therapeutic effect of ligustrazine on Sedum aizoon induced HVOD in mice. Methods： A total of 115 mice were randomly divided into 4 groups：mice in group A were intragastrically administrated with 30 mg·kg^-1·d^-1Sedum aizoon to induce HVOD and served as model group; mice in group B were given 30 mg·kg^-1·d^-1Sedum aizoon ＋ 100 mg·kg^-1·d^-1ligustrazine and served as low dose ligustrazine intervention group; mice in group C were given 30mg·kg^-1·d^-1Sedum aizoon ＋ 200 mg·kg^-1·d^-1ligustrazine and served as high dose ligustrazine intervention group; mice in group D were given 30mg·kg^-1·d^-1PBS and served as normal control group. After 30 days,all the mice were sacrificed. HE staining and Masson staining were performed for histological examination. The mRNA and protein expressions of tissue factor（ TF）,nuclear factor（ NF）-κBp65 and early growth response factor（ Egr）-1 in liver tissue were determined by RT-PCR and Western blotting,respectively. Results： HE staining and Masson staining histological examination showed that ligustrazine could obviously ameliorate the pathological injury of liver tissue in HVOD mice. Compared with group D,the mRNA and protein expressions of TF,NF-κBp65,Egr-1 were significantly increased in group A（ P 〈0. 05）. After intervention with ligustrazine,the mRNA and protein expressions of TF,NF-κBp65,Egr^（-1） were significantly decreased（ P 〈0. 05）,especially in group C,and no significant differences were found between group C and group D（ P 〈0. 05）. Conclusions：Ligustrazine has therapeutic effect on HVOD,the possible mechanism is that ligustrazine could interrupt the activation of coagulation system by reducing the expre

关 键 词：肝静脉闭塞性疾病 土三七 川芎嗪 组织因子 早期生长反应蛋白质1 NF-κBp65亚基 

分 类 号：R285.5[医药卫生—中药学]