rt-PA静脉溶栓对脑缺血大鼠血脑屏障通透性及MMP-2、MMP-9活性和表达的影响  

Effects of rt-PA intravenous thrombolysis on blood-brain barrier permeability, the expressions and the activities of MMP-2 and MMP-9 after cerebral ischemia in rats

作　　者：蔡颖源[1] 马玉苹[1] 王真真[1] 丁国宪[1] 吕秋石[2] 刘新峰[2] 陈伟贤[1] 

机构地区：[1]南京医科大学第一附属医院老年医学科,210029 [2]南京军区南京总医院神经内科,210002

出　　处：《国际脑血管病杂志》2012年第12期918-923,共6页International Journal of Cerebrovascular Diseases

基　　金：国家自然科学基金资助项目（30900452）

摘　　要：目的探讨重组组织型纤溶酶原激活剂（recombinant tissue plasminogen activator．rt-PA）静脉溶栓对脑缺血大鼠血脑屏障（blood-brainbarrier，BBB）通透性及基质金属蛋白酶（matrix metalloproteinases，MMP）-2和MMP-9活性及表达的影响。方法46只健康雄性sprague-Dawley大鼠随机分为假手术组（n=10）、大脑中动脉闭塞（middle cerebral artery occlusion，MCAO）组（n=18）和rt-PA溶栓组（n=18）。采用自体血栓栓塞法制作MCAO模型。假手术组不注入血栓栓子，MCAO组仅制作MCAO，rt-PA溶栓组在MCAO后3h给予rt-PA静脉溶栓。2,3，5-氯化三苯基四氮唑染色法检测脑梗死体积。伊文思蓝渗出法检测BBB通透性。分别采用明胶酶谱法和蛋白质印迹法检测脑组织MMP-2和MMP-9活性和表达。对各组神经功能评分、脑梗死体积、出血评分、BBB通透性以及MMP-2和MMP-9活性和表达情况进行比较。结果rt-PA溶栓组神经功能较MCAO组显著改善，脑梗死体积也显著缩小（t=7．365，P=0．005），但出血评分（t=-3．286，P=0．017）和BBB通透性（t=-3．947，P=0．029）均显著增加。假手术组MMP-2和MMP-9活性和表达水平均较低，MCAO组MMP-2（t=-45．121，P=0．000；t=-11．624，P=0．000）和MMP-9（t=-71．849，P=0．000；t=-8．992，P=0．000）活性和表达均显著性增高和上调，而rt-PA溶栓组MMP．2（t=-28．792，P=0．000；t=-3．809，P=0．013）和MMP-9（t=-53．506，P=0．000；t=-2．640，P=0．046）活性和表达较MCAO组显著性增高和上调。结论rt-PA静脉溶栓治疗后BBB通透性增加，MMP-2和MMP-9活性和表达增高和上调。MMP-2和MMP-9可能参与了BBB通透性增加，从而诱发脑缺血大鼠rt-PA静脉溶栓治疗后的出血性转化。Objective To investigate the effects of recombinant tissue plasminogen activator （rt-PA） intravenous thrombolysis on blood-brain barrier （BBB） permeability, the expressions and the activities of MMP-2 and MMP-9 after cerebral ischemia in rats. Methods A total of 40 adult male Sprague-Dawley rats were allocated into 3 groups： Sham operation group （n = 10）, middle cerebral artery occlusion （MCAO） group （n = 18）, and rt-PA thrombolysis group （n = 18）. A MCAO model was established by using autologous thromboembolism. The sham operation group did not inject any thromboembolus, the MCAO group only madeMCAO, and the rt-PA thrombolysis group received intravenous thrombolysis with rt-PA at 3 hours after MCAO. Brain infarct volume was determined by 2, 3, 5-triphenyl tetrazolimn chloride staining BBB permeability was measured by Evans blue dye leakage. The activities and the expressions of MMP-2 and MMP-9 in brain tissue were detected by Gelatin zymogaphy and Western blot, respectively. Results Compared to the MCAO group, the ne^ological function was improved sigaificantly in the rt-PA thrombolysis group, and the infarct volume was also reduced si^aificantly （t = 7. 365, P = 0. 005）. However, the hemorrhage score （t = - 3. 286, P = 0. 017） and BBB permeability （t = - 3. 947, P = 0. 029） were increased significantly. The activities and the expressions of MMP-2 and MMP-9 in the sham operation group were lower. The activities and the expressions of MMP-2 （t = -45. 121, P = 0. 000; t = -11. 624, P = 0. 000） and MMP-9 （t= -71.849, P= 0.000; t= -8. 992, P= 0. 000） in the MCAO group were increased and upregulated significantly. Compared to the MCAO group, the activities and the expressions of MMP-2 （t = - 28. 792, P = 0. 000; t = -3. 809, P =0. 013） and MMP-9 （t = -53.506, P =0. 000; t = -2. 640, P =0. 046） in the rt-PA thrombolysis group were increased and upregulated significantly. Conclusions After rt-PA intravenous thrombolytic therapy, the BBB permeability was increased. T

关 键 词：组织型纤溶酶原激活物 脑缺血 基质金属蛋白酶9 基质金属蛋白酶2 血脑屏障 血 栓溶解疗法 脑出血 疾病模型 动物 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]