缓激肽受体抑制剂对脑缺血再灌注大鼠的脑保护作用

为了探讨缓激肽及其受体在脑缺血急性期对血脑屏障通透性及炎症因子分泌的影响,本研究采用线栓法制作大鼠大脑中动脉梗塞(MCAO)模型,分别应用缓激肽B1和B2受体的特异性抑制剂,在缺血再灌流后24h进行动物行为学评分,TTC染色计算梗死体积,伊文斯蓝染色检测血脑屏障通透性,透射电镜观测血脑屏障超微结构的变化,ELISA对缺血区IL-1β、TNF-α、PGE2进行测定。结果显示:缓激肽B1和B2受体抑制剂能够改善脑缺血大鼠急性期行为学评分、缩小梗死体积、降低血脑屏障通透性、维持血脑屏障结构完整、抑制炎症因子分泌,缓激肽B2受体抑制剂的上述效果优于B1受体抑制剂。以上结果提示缓激肽在脑缺血急性期可以加重脑损伤,其受体的特异性抑制剂可以减轻脑损伤。

THE NEUROPROTECTIVE EFFECT OF BRADYKININ RECEPTOR ANTAGONISTS IN CEREBRAL ISCHEMIA/REPERFUSION RATS

In order to investigate the effect of bradykinin and bradykinin receptor on the permeability of blood-brain barrier (BBB) and secretion of inflammatory factors during the acute phase of cerebral ischemia, the transient middle cerebral artery occlusion (MCAO) model was made following the intraluminal thread technique. Bradykinin B1 or B2 receptor antagonists were administrated immediately after reperfusion. Twenty-four hours after reperfusion, neurological function was appraised by neurological severity scores (NSS), infarct volume was determined by TTC staining, permeability of BBB was measured by Evans blue extravasation, the ultrastructural changes of BBB was observed by transmission electron microscope and the concentrations of IL-1β, TNF-α and PGE2 in ischemic tissues were measured by ELISA. The results showed that bradykinin receptor antagonist can dramatically improve the neurological function, decrease the infarct volume and permeability of BBB, maintain the integrity of BBB, suppress the secretion of inflammatory factors, with a more obvious effect for B2 receptor antagonist. These results suggest that in the acute phase of cerebral ischemia, bradykinin may act as a detrimental factor, whose damage function could be alleviated by its specific receptor antagonists.