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

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3 h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）mm3]及常规剂量t-PAm[（68.3±17.2）mm3]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。

Abstract:

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-PAm) group. The rats of the three groups were treated separately 3 hours after thrombosis in middle cerebral artery. Volume of infarction, neurologic scores and severity of hemorrhage were observed 24 hours after treatment. The protective role of t-PAm for brain tissue was evaluated through neutrophil infiltration 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-PAm 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-PAm 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.