亚低温联合镁剂对脑缺血再灌注大鼠保护作用的研究

Protective Effect of Mild Hypothermia Combined with MgSO_4 on the Rats with Cerebral Ischemia/Reperfusion

目的:rt-PA溶栓为缺血性卒中最有效的治疗方法,脑血流再通后挽救濒临死亡的神经细胞同时,也可能发生更为严重而持久的脑缺血再灌注损伤。本研究探讨联合应用局部亚低温(32-35℃)及硫酸镁对局灶性脑缺血再灌注大鼠的保护作用及其可能机制。方法:通过线栓法建立大鼠大脑中动脉阻塞(MCAO)及再通模型,将50只雄性Wistar大鼠随机分为假手术组、常温组、亚低温组、硫酸镁组、亚低温+硫酸镁组,每组10例,采用Longa神经功能评分、TTC染色、干湿重法、TUNEL技术,检测和比较各组脑缺血再灌注后大鼠的神经功能、脑梗死体积、脑组织含水量及凋亡细胞数。结果:与常温组相比,亚低温组与亚低温+硫酸镁组的梗死体积、神经功能评分、脑组织含水量、凋亡细胞数均明显降低,差异有显著意义(P<0.05);而与亚低温组相比,亚低温+硫酸镁组局灶脑缺血大鼠的脑梗死体积、神经功能评分、脑组织含水量、凋亡细胞数均显著减少,差异有显著意义(P<0.05)。结论:与单独应用亚低温相比,局部亚低温与硫酸镁联合应用,对局灶性脑缺血再灌注大鼠可发挥更有效的脑保护作用。其机制可能与抑制脑缺血再灌注后凋亡及减轻脑水肿有关。二者联用可能为缺血性卒中患者提供一种减轻溶栓后再灌注损伤的有效脑保护方法。

Objective： The most effective therapy in ischemic stroke is rt-PA thrombolysis, which may not only rescue the salvageable neurons, but also cause more severe and permanent ischemia-reperfusion injury. Our study aimed to investigate the protective effect of focal mild hypothermia combined with MgSO4 on the rats with focal cerebral ischemia/reperfusion and its possible mechanism. Methods： The middle cerebral artery occlusion（MCAO）/reperfusion models of rat were achieved by an intraluminal filament. Fifty male adult Wistar rats（each group n=10） were randomly divided into sham-operated group, normothermia ischemia group,MgSO4 group, mild hypothermia group and mild hypothermia＋ MgSO4 group. The neurological function, infarct volumes, brain water content and apoptotic cell numbers in the ischemic cortex were assessed by Longa neurological scores, TTC stain, weight？（W/D） ratio and TUNEL. Results： Compared with normothermia group, the neurological scores, infarct volumes, water content and apoptotic cell numbers markedly decreased in hypothermia group and hypothermia＋ MgSO4group（P〈0.05）; Compared with mild hypothermia group,the neurological scores, infarct volumes, water content and apoptotic cell numbers markedly decreased in hypothermia＋ MgSO4group（P0.05）. Conclusions： Focal mild hypothermia combined with MgSO4 is more effective in protection on the rats with focal cerebral ischemia/reperfusion than mild hypothermia. The protective effect is partly due to reduce apoptosis and brain edema. It is possible that mild hypothermia combined with MgSO4 which can reduce ischemia/reperfusion injury will provide an effective protective method in patients after rt-PA thrombolysis.