中国中药杂志

2008, (18) 2124-2128

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一种热毒诱导的血栓形成动物模型的建立
Development of virulent heat-evil-induced thrombosis animal model

梁爱华;刘婷;李春英;薛宝云;王金华;
LIANG Ai-hua,XUE Bao-yun,WANG Jin-hua,LI Chun-ying (1.Macau University of Science and Technology,Macau,China;2.Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

摘要(Abstract):

目的:建立一种热毒诱导的血栓形成动物模型,为血栓性疾病的热毒病因病机研究、清热解毒法治疗血栓性疾病的作用及其作用机制研究以及清热解毒药的抗血栓活性筛选和临床前研究提供合适的动物模型。方法:将大鼠随机分成对照组和模型组。模型组动物先腹腔注射Ca 5 mg/鼠,16 h后再静脉注射LPS 50μg.kg-1。于造模后不同时间观察尾部血栓形成情况,测定外周血白细胞数量、血浆TXB2,6-keto-PFG1,αTNF-α和IL-6水平、白细胞黏附分子CD11b/CD18表达以及尾血管P-选择素表达。结果:造模后,可在大鼠尾部远端形成稳定的血栓,动物血液中的炎性因子TNFα和IL-6大量产生,白细胞黏附分子CD11b/CD18和血管内皮细胞P-选择素等表达明显增高,有较多的白细胞黏附于血管壁,外周血白细胞计数减少,提示本模型的血栓形成与炎症反应有关。结论:本模型由内毒素这种外源性热毒诱导,体内产生明显的炎症反应病理过程,提示热毒是本模型的重要病机。
Objective: To develop a virulent heat-evil-induced thrombosis animal model,and provide a rational animal model for pathogeny and pathogenesis research of thrombosis-related diseases,anti-thrombosis activity screening and pre-clinical studies of CAHT formula.Method: SD rats were pretreated with carrageenin(Ca) intraperitoneal injection,followed by intravenous injection of endotoxin(LPS from E.coli O111: B4) 50 μg·kg-1 16 h later.Thrombosis in rat tails were observed during 12-24 h after injection of LPS.The inflammatory mechanism of this model were investigated by analyzing serum level of TNF-α,IL-6,TXB2 and 6-keto-PGF1α,CD11b/CD18 expression of white blood cells(WBC) and P-selectin expression of vessel walls.Result: In LPS/Ca model group,thrombosis can be clearly observed in the distal part of rat tails after 12-24 h of LPS/Ca treatment.High level of TNF-α and IL-6 can be measured in serum.The expression of CD11b/CD18 in WBC and P-selectin in vessel endothelium significantly increased and the number of WBC in peripheral blood markedly decreased shortly after LPS/Ca treatment.The adherence of white blood cells to vessel endothelium which can be seen by microscope mainly contributed to the decrease of WBC.The results indicated that there was obvious inflammation after treatment with LPS/Ca,suggesting that inflammation was the key mechanism for this model.Conclusion: This model was developed through treatment of LPS in combination with Ca,of which LPS is considered to be an exotic virulent heat-evil in TCM,while the inflammatory molecules produced in this model,such as TNF-α,IL-6,CD11b/CD18 and P-selectin belong to internal virulent heat-evils,so this animal model consists of pathogeny and pathogenesis of virulent heat-evils.virulent heat-evil.

关键词(KeyWords): 血栓形成;热毒;病因病机;动物模型;炎症
thrombosis;pathogeny and pathogenesis;animal model;inflammation

Abstract:

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基金项目(Foundation): 国家自然科学基金项目(39870910,39970902);; 国家重大基础研究计划(973)项目(G1999054407,2006CB504700)

作者(Author): 梁爱华;刘婷;李春英;薛宝云;王金华;
LIANG Ai-hua,XUE Bao-yun,WANG Jin-hua,LI Chun-ying (1.Macau University of Science and Technology,Macau,China;2.Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

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