组织型纤溶酶原激活物突变体对鼠急性脑梗死及脑组织保护作用实验研究  

Protective effect of tissue type plasminogen activator mutant on acute cerebral thrombosis and cerebral tissue in rats

作　　者：侯沛秋 祝丹[1] 唐曦[2] 林川[3] 曾大奎[3] 

机构地区：[1]成都医学院医学影像系,四川成都610500 [2]成都医学院第一附属医院医学影像系,四川成都610500 [3]四川省宜宾市第二人民医院肿瘤二科,四川宜宾644000

出　　处：《中国现代医学杂志》2017年第4期22-26,共5页China Journal of Modern Medicine

摘　　要：目的评价新型组织型纤溶酶原激活物突变体(t-PAm)对鼠急性脑梗死溶栓作用及脑组织保护作用。方法 84只成年Wistar大鼠随机分为对照组、组织型纤溶酶原激活物组(t-PA)、低剂量组织型纤溶酶原激活物突变体组(低剂量t-PAm组)及常规剂量组织型纤溶酶原激活物突变体组(常规剂量t-PAm组),大脑中动脉血栓形成3h后进行相应治疗。观察溶栓24 h后脑梗死面积、神经损伤评分、脑出血的情况,并通过中性粒细胞浸润及蛋白酶激活受体1(PAR-1)浓度的变化了解t-PAm对脑组织的保护作用。结果梗死后应用低剂量t-PAm[(108.5±27.3)mm^3]及常规剂量t-PAm[(68.3±17.2)mm^3]组梗死面积均较对照组降低,同时梗死面积与神经评分有明确的相关性(r=0.613,P=0.000),且低剂量t-PAm在溶栓的同时没有明显增加脑出血的概率。t-PAm还减少髓过氧化物酶的生成,并与t-PA组相比减少PAR-1的生成(P<0.001)。结论新型组织型纤溶酶原激活物突变体有较好的溶栓作用,同时对缺血脑组织有明显的保护作用。Objective To evaluate the thrombolytic and brain-protective effect of new tissue plasminogen activator mutant in rat model of acute cerebral thrombosis. Methods Eighty-four adult Wistar rats were randomly divided into control group, tissue-type plasminogen activator （t-PA） group, low-dose tissue plasminogen activator mutant （low- dose t-PAm） group and conventional-dose tissue plasminogen activator mutant （regular-dose t-PAre） group. The rats of the three groups were treated separately 3 hours after thrombosis in middle cerebral artery. Volume of infarction, neurologie scores and severity of hemorrhage were observed 24 hours after treatment. The protective role of t-PAm for brain tissue was evaluated through neutrophil infihration and the change in the concentration of PAR-1. Results Volume of infarction in the low-dose t-PAm group and the regular-dose t-PAre group was significantly smaller than that in the control group [（108.5± 27.3） mm3 and （68.3 ±17.2） mm3 vs （323.4 ± 42.3） mm3], and the neurologic scores were evidently correlated with the volume of infarction （r = 0.613, P = 0.000）, while the incidence of cerebral hemorrhage in the low-dose t-PAm group was not significantly increased. T-PAre also reduced the production of myeloperoxidase, as well as the production of PAR-1, compared with the t-PA group （P 〈 0.001）. Conclusions New tissue plasminogen activator mutant shows better thrombolytic effect with significant protection for ischemic brain tissue.

关 键 词：尿激酶 血栓 组织型纤溶酶原激活物 突变体 

分 类 号：R-332[医药卫生]