糖酐酯对脑栓塞大鼠溶栓治疗影响的研究

Effects of thrombolytic therapy combined with dextran sulfate in rat with cerebral embolism

目的 观察糖酐酯对脑栓塞大鼠白细胞浸润的抑制作用及对溶栓治疗后梗死灶体积、细胞凋亡等的影响。方法 用自体血栓子栓塞大鼠大脑中动脉 0 .5h后 ,静脉给予糖酐酯或生理盐水 ,2h或 4h后应用尿激酶溶栓治疗 ,12h或 2 4h后 ,采用TTC染色测定梗死灶大小 ,免疫组化法检测白细胞浸润和细胞间黏附分子 1(ICAM 1)表达 ,TUNEL法检测细胞凋亡 ,透射电镜观察血脑屏障 (BBB)及细胞坏死。结果 联合溶栓组与单纯溶栓组比较 ,梗死灶减小 (P <0 .0 5 ) ,缺血周边区浸润白细胞数和凋亡细胞数明显减少 (均P <0 0 1) ,BBB损伤及细胞坏死程度减轻 ,颅内出血发生例数减少。但ICAM 1表达两组比较无显著性差异 (P >0 0 5 )。结论 糖酐酯能明显抑制白细胞浸润 ,其作用机制与ICAM 1表达无关 ;抑制白细胞浸润可以增强溶栓治疗疗效、保护BBB和减少溶栓治疗后神经细胞凋亡。

Objective To study the effect of dextran sulfate inhibiting leukocytes infiltration and infarct size,and apoptosis in rats with cerebral embolism.Methods Using one's blood emboli,dextran sulfate (4 mg/kg) or saline was intravenously administered after half an hour ischemia and urokinase (5000 U/kg) was injected after 2h or 4h ischemia in rat embolic stroke models.At 12h or 24h after ischemia,the infarct size were measured by TTC staining.ICAM-1 expression and leukocytes infiltration were evaluated by immunohistochemistry, apoptosis were detected by TUNEL;blood-brain barrier(BBB) and cell necrosis were observed by electromicroscopy.Results combined thrombolytic group compared with pure thrombolytic group,the infarct focus decreased(P< 0.05) leukocytes infiltration in margin of ischemia as well as apoptosis of neurons were significantly reduced(P<0.01), injuries of BBB and cell necrosis were lightered, the patients with intracranial hemorrhage decreased, but there was no remarkbale difference between the two groups(ICAM-1 expression)Conclusion Combined with thrombolysis,dextran sulfate could significantly inhibit leukocytes infiltration and apoptosis of neurons.its mechanism doesn't relate to ICAM-1 expression.Inhibiting leukocyte infiltration may enhance the efficacy of thrombolysis therapy,and protect blood cerebral barrier and decrease apoptosis of neurons after thrombolytic therapy.