缺血后处理对新生大鼠缺氧缺血性脑损伤的影响

The influence of ischemic postconditioning for hypoxic-ischemic brain damage on newborn rats

目的探讨缺血后处理(IPostc)对新生大鼠缺氧缺血性脑损伤(HIBD)可能的神经保护作用及其机制。方法以7日龄SD大鼠为研究对象,随机分为假手术组、HIBD组、IPostcⅠ组(15 s再灌注/15 s夹闭×3个循环)及IPostcⅡ组(30 s再灌注/10 s夹闭×3个循环),每组根据缺氧缺血后时间分为0、6、12、24 h及48 h 5个亚组,每个亚组15只。应用右侧颈总动脉夹闭联合低氧(8%O2+92%N2)建立HIBD模型,监测脑组织形态学变化,比较超氧化物歧化酶(SOD)、丙二醛(MDA)、脑组织含水量及水通道蛋白4(AQP4)mRNA相对表达量随时间的变化规律。结果经缺氧缺血处理的大鼠均出现典型的神经行为学异常、形态学和生化指标的变化。IPostcⅠ组SOD活性显著改善,MDA含量降低,脑组织含水量及AQP4 mRNA相对表达量降低,在6 h以后作用显著,差异有统计学意义(P<0.05)。而IPostcⅡ组无明显改善作用。结论缺血后处理对新生大鼠HIBD具有一定的神经保护作用,其机制与减轻氧化应激损伤及脑水肿有关。

Objective To study the neuroprotective effects of ischemic postconditioning（ IPostc） for hypoxic ischemic brain damage（ HIBD） and possible mechanisms on newborn rats.Methods Seven-day-old SD rats were randomly assigned into four groups： control group,HIBD group,IPostcⅠgroup（ 15 s reperfusion /15 s clipping × 3 cycles） and IPostc Ⅱ group（ 30 s reperfusion /10 s clipping × 3 cycles）,then subdivided into five subgroups（ 0 h,6 h,12 h,24 h,48 h）. HIBD model was established combining occlusion of right common carotid artery with hypoxia（ 8% O2＋ 92% N2）. The brain pathology,SOD and malondialdehyde（ MDA） levels,water content,and AQP4 mRNA expression of brain tissue were studied. Results The HIBD rats showed typical neurobehavioral abnormalities and significant changes in pathological morphology and biochemical indicators. The IPostc Ⅰ group showed significantly improved SOD activity,reduced MDA and water content,and decreased AQP4 mRNA expression. The differences were statistically significant among these groups（ P〈0. 05） except for 0 h subgroup. Conclusions Ischemic postconditioning may have neuroprotective effects on newborn HIBD rat,which may be related to reduced oxidative stress and cerebral edema.