溶栓联合神经保护剂对大鼠脑梗死的保护作用

Protective effects of the combinative therapy with thrombolysis and neuroprotective on cerebral infarction in rats

目的观察尿激酶(UK)溶栓联合依达拉奉(ED)治疗对大鼠急性脑梗死区微血管基底膜纤维连接蛋白(fibronectin,FN)表达的影响,探讨溶栓联合神经保护剂在急性脑梗死治疗中的作用及可能机制。方法自体血栓栓子法制作大鼠左侧大脑中动脉阻塞(MCAO)模型,实验动物随机分为4组:假手术组(Sham组),生理盐水对照组(NS组),尿激酶溶栓组(UK组),尿激酶+依达拉奉组(UK+ED组)。各组缺血24h后分别采用TTC染色、HE及免疫荧光法观察大鼠脑组织梗死情况、病理变化及微血管基底膜FN表达状况。结果手术后24h,假手术组未见脑梗死组织;UK与UK+ED组脑梗死体积均较NS组缩小(P均<0.01);UK+ED组又比UK组的梗死体积小(P<0.01)。免疫荧光结果显示,FN在缺血组的表达均减弱(P均<0.01),以UK组减弱最为明显,UK+ED组减弱最轻,各组间差异有显著性(P<0.05)。结论依达拉奉可能通过减轻脑缺血尿激酶溶栓后的基底膜损伤,减少脑梗死体积,从而加强溶栓治疗的脑保护作用。

Objective To investigate the effect of urokinase（UK） thrombolysis in combination with edaravone on the microvascular basallamina （fibronectin, FN）on acute cerebral ischemia in rats. To approach the possible mechanism of thrombolysis in combination with neuroprotective agent. Methods Sprague-Dawley rats were subjected to middle cerebral artery occlusion（MCAO） by autologous blood embolism. Rats of four groups were studied： rats suffered sham operation（Sham group）, untreated ischemia controls （NS group）, rats that received UK after ischemia（UK group） ,rats that received urokinase and edaravone（UK＋ ED group）. The infarction volume of brain was investigated by 2,3,5-triphenyl tetrazolium chloride（TTC） coloring. The histological morphlogical damage of brain was investigated by hematoxylin-eosin（HE）staining. The expression of FN of the four groups was analyzed by immunofluorescence 24h after ischemia. Results Cerebral ischemia couldnot be seen in sham operation. Infarction volume was lower both in UK and UK＋ ED compared with NS group（P〈0.01）, UK＋ ED group was significantly lower （P〈0.01）. Immunofluorescence revealed basal lamina FN degradation in ischemic groups （all P〈0.01）, the expression was weaker in UK than NS and UK＋ED group （P〈0.05） ,NS was weaker than UK＋ED（P〈0.05）. Conclusion Edaravone probably enhanced the expressions of fibronectin and relieved brain damage after ischemia/reperfusion. Thus,it has the effects of certain neural protection in thrombolysis.