缺血后处理联合远隔缺血后处理对大鼠局灶性脑缺血再灌注损伤的影响

Effects of combination of ischemic postconditioning and remote ischemic postconditioning on focal cerebral ischemia-reperfusion injury in rats

目的探讨缺血后处理联合远隔缺血后处理对大鼠局灶性脑缺血再灌注损伤的影响。方法成年雄性sD大鼠86只，体重270～330g，随机分为5组，假手术组（Ⅰ组，n=19）仅实施手术，不行缺血再灌注；缺血再灌注组（Ⅱ组，n=19）阻断右侧大脑中动脉缺血1．5h，再灌注24h制备大鼠局灶性脑缺血再灌注损伤模型；Ⅲ组（n=16）再灌注前脑缺血30s，再灌注30S，重复3次；Ⅳ组（n=16）再灌注前右侧股动脉缺血5min恢复灌注；Ⅴ组（n=16）再灌注前行缺血后处理及远隔缺血后处理。于再灌注2和24h时行神经功能缺损评分（NDS评分）；再灌注24h时断头取脑，测定脑梗死面积，检测脑组织微管相关蛋白2（MAP2）的表达水平；股静脉注射异硫氰酸一右旋糖酐，断头取脑，行共聚焦扫描，以对侧作为对照。结果与Ⅰ组比较，Ⅱ组、Ⅲ组、Ⅵ组和Ⅴ组NDS评分和缺血侧脑梗死面积百分比明显升高，缺血侧脑组织MAP2表达水平、血浆容量、微血管直径和长度明显降低（P〈0．05）；与Ⅱ组比较，Ⅲ组、Ⅳ组和Ⅴ组NDS评分和缺血侧脑梗死面积百分比明显降低，缺血侧脑组织MAP2表达水平、血浆容量、脑微血管直径和长度明显增加（P〈0．05）。结论缺血后处理联合远隔缺血后处理可减轻大鼠局灶性脑缺血再灌注损伤，其效果与两者单独应用时相似。

Objective To investigate the effects of combination of ischemic postconditioning （IPC） and remote IPC on the focal cerebral ischemia-reperfusion （I/R） injury in rats. Methods Eighty-six adult male SD rats were randomly divided into 5 groups： sham operation group （group Ⅰ , n = 19）, I/R group （group Ⅱ, n = 19）, IPC group （group [Ⅲ, n = 16）, remote IPC group （group Ⅳ, n = 16）, and IPC ＋ remote IPC group （group Ⅴ , n = 16）. Focal cerebral I/R was produced by occlusion of the right middle cerebral artery （MCA） for 1.5 h followed by 24 h of reperfusion. In group I , operation was performed but focal cerebral I/R was not produced. In group Ⅲ , the rats were subjected to 3 episodes of 30 s ischemia at 30 s intervals before 24 h of reperfusion. In group Ⅳ , after 1.5 h of the right MCA occlusion, remote IPC was performed by occluding the right femoral artery for 5 min before 24 h of reperfusion. In group Ⅴ , IPC and remote IPC were performed as described in group Ⅲ and Ⅳ respectively before 24 h of reperfusion. The neurologic deficit scores （NDSs） were measured at 2 and 24 b of reperfnsion. Ten rats in each group were decapitated at 24 h of reperfusion and brains rapidly removed for measuring the cerebral infarct size （IS）. The expression of microtubule-associated protein 2 （MAP2） were detected. The animals received iv injection of fluorescein isothiocyanate （ FICT）-dextran via the femoral vein 1 min before decapitation for laser confocal scanning. The contralateral side was served as control. Results As compared with group Ⅰ, the NDSs and cerebral IS on the ischemic side were significantly increased, and the cerebral expression of MAP2, plasma volume of the cerebral tissues, and diameter and length of the cerebral microvessel on the ischemic side significantly decreased in group Ⅱ , Ⅲ, Ⅳ and Ⅴ （ P 〈 0.05 ） . As compared with group Ⅱ, the NDSs and cerebral IS on the ischemic side were significantly decreased, and the cerebral expression of MAP2, plasma volume of the cerebral tissues, and diameter and length of the cerebral microvessel on the ischemic side significantly increased in group Ⅲ, Ⅳ and Ⅴ （ P 〈 0.05 ）. Conclusion Although the combination of IPC and remote IPC can attenuate the focal cerebral I/R injury in rats, the efficacy is similar to that of either of them alone.