光化学法诱导大鼠冠状动脉血栓模型的建立和应用  

Establishment of rat coronary thrombosis model by photochemistry

作　　者：郝春华[1] 王维亭[1] 宋书辉[1] 赵专友[1] 汤立达[1] 

机构地区：[1]天津药物研究院药代与药效动力学重点实验室,天津300193

出　　处：《中国药理学通报》2012年第1期143-146,共4页Chinese Pharmacological Bulletin

基　　金：系列化;国际化的国家生物医药国际创新园药物综合研发大平台(No 2009zx09301-008);"十一五"重大新药创制科技重大专项课题"国家生物医药国际创新园(天津)创新药物孵化基地建设药效学评价研究平台"(No2010ZX09401-307)

摘　　要：目的建立光化学法诱导大鼠冠状动脉血栓致心肌梗死模型。方法大鼠分为激光和化学单独刺激组、联合刺激组和重组葡激酶处理组,通过注射光敏剂四氯四碘荧光素二钠(虎红)后激光照射冠状动脉形成血栓致心肌梗死动物模型,比较各组血管栓塞程度以及心电图Ⅱ导联ST段高度变化选择出最佳模型。并用该模型评价重组葡激酶溶栓作用效果。结果相对于单独刺激组,联合刺激组心脏激光照射处均出现明显损伤病灶。HE染色心肌细胞肿胀,排列紊乱,动静脉内均见血栓。心电图出现不同程度心律失常,ST段抬高。其中注射40 mg.kg-1虎红后照射15 min心律失常出现时间较早,心电图ST段抬高幅度高、维持时间长,而且死亡率低,为本研究中最佳光化学法冠状动脉血栓模型。重组葡激酶处理组能够部分溶解动静脉血管内血栓,减小血栓面积(P<0.01),抑制ST段抬高(P<0.05～0.01)。结论该文建立了最佳光化学法诱导大鼠冠状动脉血栓模型,适于溶栓药物研发评价。Aim To establish a rat coronary thrombosis model induced by photochemistry.Methods Rats were divided as single stimulation group,conjunct stimulation group and recombinant staphylokinase group.Laser irradiation was performed after the injection of photosensitizer rose bengal to achieve coronary thrombosis for myocardial infarction,whereafter the best model was chosen by comparing the intravascular embolism and ST segment elevation.The effect of recombinant staphylokinase was also evaluated.Results Compared with the single stimulation group,there was significant injury at the heart of the conjunct stimulation group.The swelled and disordered myocardial fiber and thrombus inside the arterial and venous were seen in HE staining.Meanwhile ST segment elevated to some extent in ECG.The model of 15 min irradiation after the injection of 40 mg·kg-1 rose bengal was the best model because of the earlier arrhythmia,higher ST segment elevation,longer time endurance and lower death rate.Recombinant staphylokinase could reduced thrombus area（P0.01） and inhibited ST segment elevation（P0.05～0.01）.Conclusion A best model of rat coronary thrombosis is established by photochemistry,which is applicable to antithrombotic drugs research.

关 键 词：激光 虎红 冠状动脉 血栓 心肌梗死 重组葡激酶 

分 类 号：R-332[医药卫生] R322.12