一种改进的卒中溶栓出血转化的大鼠血栓栓塞模型  

A modified rat model of thromboembolism for study of hemorrhagic transformation in stroke after intravenous thrombolysis

作　　者：陈昕[1] 郭志良[1] 叶瑞东[1] 姜永军[1] 俞书红 肖露露[1] 孙文[1] 李华[1] 朱武生[1] 徐格林[1] 刘新峰[1] 

机构地区：[1]南京大学医学院附属金陵医院(南京军区南京总医院)神经内科,南京医学硕士研究生210002

出　　处：《医学研究生学报》2015年第11期1171-1174,共4页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81171099);江苏省"六大人才高峰"资助项目(2014-WSW-043)

摘　　要：目的目前尚缺乏与临床接近的重组组织型纤溶酶原激活剂(recombinant tissue-type plasminogen activator,rt PA)溶栓后出血转化的动物模型。文中建立一种贴近临床的用于研究卒中溶栓后出血转化的大鼠脑血栓栓塞模型。方法文中通过对栓子注入部位及溶栓时间进行改进,将60只SD大鼠按随机数字表法分为假手术组、脑栓塞组与rt PA溶栓组。取大鼠股动脉血制备体外血栓,脑栓塞组与rt PA溶栓组将血栓注入颈内动脉建立脑血栓栓塞模型,假手术组注入含BSA的PBS。栓子注入5 h后,rt PA溶栓组静脉溶栓,脑栓塞组和假手术组则注入等渗盐水。栓子注入24 h后对大鼠进行神经功能评分,大鼠心脏灌流后处死,取脑进行TTC染色,评价梗死体积与脑水肿程度,并采用分光光度法检测出血体积。结果 rt PA溶栓组与脑栓塞组的梗死体积[(29.29±4.204)%vs(27.89±3.91)%,P=0.810 3]、脑水肿程度[(12.43±1.66)%vs(7.13±2.04)%,P=0.063 2]、神经功能评分[(3.35±0.27)分vs(2.80±0.28)分,P=0.174)]差异均无统计学意义,但出血体积溶栓组明显高于脑栓塞组[(17.55±2.20)μL vs(3.82±0.86)μL,P<0.01]。结论溶栓后出血转化的大鼠脑血栓栓塞模型能形成与临床rt PA静脉溶栓发生出血转化的病理改变,稳定性和重复性较好,可用于rt PA溶栓出血转化发病机制的相关研究。Objective The purpose of this study was to establish a rat model of thromboembolism for the study of hemorrhagic transformation after intravenous thrombolysis with the recombinant tissue plasminogen activator（ rt PA）. Methods Sixty SpragueDawley rats were randomly divided into a sham operation,a cerebral embolism,and an rt PA group. Thrombus was prepared in vitro with the rat femoral artery blood and injected into the internal carotid artery of the rats in the cerebral embolism and rt PA groups to establish a model of embolic focal cerebral ischemia,while the animals of the sham operation group injected with BSA. Five hours later,the rats in the rt PA group received rt PA and those in the cerebral embolism and sham operation groups the injection of isotonic saline solution. At 24 hours after embolus injection,the neurological deficit score was obtained. The rats were sacrificed after cardiac perfusion and their brains removed for triphenyltetrazolium chloride staining,assessment of the infarct volume and cerebral edema,and calculation of the hemorrhage volume by spectrophotometric hemoglobin assay.Results The hemorrhage volume was significantly higher in the rt PA than in the cerebral embolism group（ [17. 55 ± 2. 20] μL vs[3. 82 ± 0. 86] μL,P 0. 01）,but there were no statistically significant differences between the two groups in the infarct volume（ [29. 29 ± 4. 204]% vs [27. 89 ± 3. 91]%,P = 0. 810）,cerebral edema（ [12. 43 ± 1. 66]% vs [7. 13 ± 2. 04]%,P = 0. 0632）,and neurological deficit score（ 3. 35 ± 0. 27 vs 2. 80 ± 0. 28,P = 0. 174）. Conclusion The rat model of thromboembolism,with a high stability and reproducibility,can be used for the pathogenesis-related studies of hemorrhagic transformation after thrombolysis with rt PA.

关 键 词：脑卒中 溶栓 出血转化 大鼠模型 

分 类 号：R743.3[医药卫生—神经病学与精神病学]