川芎嗪对肿瘤介导的血液高凝的影响  

The effect of Ligustrazine on tumor-mediated hypercoagulability

作　　者：王生[1] 赵杨[1] 陶丽[1] 王爱云[1] 陈文星[1] 郑仕中[1,2] 陆茵[1,2] 

机构地区：[1]南京中医药大学药学院 [2]江苏省中药药效与安全性评价重点实验室,南京中医药大学中药学一级学科,江苏南京210046

出　　处：《中国药理学通报》2012年第5期709-715,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81173174);江苏省自然科学基金资助项目(No BK2010085;210562);江苏省国际合作项目(No SBZ200900175);江苏省教育厅重大专项(No 09KJA360002);江苏省六大人才高峰课题A类第五批项目资助(No 08-A-012);江苏省中医药局项目(No LZ09022);江苏省中药药效与安全性评价重点实验室开放课题(No P09013);江苏省普通高校研究生科研创新计划项目(No 2010-469;2010-471);江苏高校优势学科建设工程资助项目

摘　　要：目的研究川芎嗪抗肿瘤转移作用与改善肿瘤介导的高凝状态两者之间的相关性。方法采用C57BL6小鼠的实验性转移模型,考察川芎嗪体内对肿瘤血行转移的影响,通过血液APTT、PT、TT、FIB检测考察肿瘤对凝血时间的影响及药物对其的改善作用,同时通过ELISA方法检测血浆t-PA、u-PA、PAI反映纤溶系统的活性变化,测定血浆中纤维蛋白肽A反映纤维蛋白的生成情况,检测血浆中FXⅢ来反映纤维蛋白的稳定程度。结果体内川芎嗪72 mg·kg-1能够抑制B16F10实验转移,明显减少肺转移结节数量。实验性转移模型组与正常组相比,凝血时间明显缩短,表现出血液高凝状态,给予川芎嗪8、24、72 mg·kg-1,不同时间均可以不同程度的延长APTT、PT、TT、FIB,并能抑制纤维蛋白的形成和稳定,进而改善肿瘤引起的血液高凝。结论肿瘤转移会引起血液的高凝,且随着转移时间的延长,血液高凝程度加剧。川芎嗪能够改善肿瘤介导的高凝状态,可能与其抗肿瘤转移作用相关。Aim To study the association between antimetastasis and improvement of tumor-mediated hypercoagulability of Ligustrazine of the main component of traditional Chinese medicine Chuanxiong.Methods The experimental metastasis model was used to study the overall efficacy of anti-metastasis of Ligustrazine.The APTT,PT,TT,FIB were tested to evaluate the effect of tumor on coagulation system and improvement of Ligustrazine.The change in the activity of fibrinolytic system was detected plasma level of t-PA,u-PA,PAI by Elisa kit.Fibrin formation was assessed by detecting plasma fibrinopeptide A（FPA） by FPA Elisa kit.The FXIII Elisa Kit was used to detect the stability of fibrin.Results Ligustrazine 72 mg·kg-1 inhibited B16F10 experimental metastasis in vivo,a significant reduction in the number of lung nodules.Clotting time of experimental metastasis model group was significantly reduced compared with normal group,showing hypercoagulability.The coagulation time of APTT,PT,TT,FIB was extended to some different extent after treatment by Ligustrazine 8 mg·kg-1,24 mg·kg-1,72 mg·kg-1 at 7,14,21th day.Besides,Ligustrazine could inhibit fibrin formation and stability,thereby improving tumor-induced hypercoagulability.Conclusions Tumor metastasis can cause blood coagulation and activate blood system,and with the transfer time extend,the hypercoagulability is more serious.Ligustrazine can inhibit tumor metastasis which may be related to the improvement of the tumor-mediated hypercoagulable state.

关 键 词：血液高凝 川芎嗪 纤维蛋白原 实验性转移 肿瘤 纤溶系统 

分 类 号：R-332[医药卫生] R284.1