肢端缺血预处理对缺血性脑损伤保护作用的初探

Protective effects of lim ischemic preconditioning pretreatment to the brain after cerebral ischemic injury

目的通过观察肢端缺血预处理(LIP)对大鼠脑缺血性损伤后炎症反应及海马区神经元细胞的影响,探讨LIP对脑缺血的保护作用。方法选取36只SD大鼠,实验组(LIP组)15只、缺血组15只和对照组6只。实验组和缺血组设立5个时间点:6h、12h、24h、48h和72h,每点3只。通过线栓法建立大鼠大脑中动脉阻塞(MCAO)的局灶性脑缺血模型及LIP法建立脑缺血耐受模型,观察并计算每组大鼠的神经功能缺损评分(NSS)、脑组织形态学与组织学改变、炎性细胞计数以及神经元密度的变化。结果缺血组和实验组在各时间点的NSS均无统计学差异。实验组脑组织学病理改变程度明显轻于缺血组;在24h、48h和72h时间点,实验组炎性细胞计数明显少于缺血组,海马CA1区正常神经元细胞明显多于缺血组,且两组相比均有统计学差异(P<0.05)。结论 LIP诱导脑缺血耐受,可以减轻脑部炎症反应和延迟海马区神经元死亡,从而减轻缺血后脑组织损伤,对缺血性脑损伤有一定的保护作用。

Objective To investigate whether limb ischemic preconditioning （LIP）pretreatment has protective effects to the brain after cerebral ischemic injury by investigating the effects of LIP pretreatment on anti- inflammation and apoptosis of pyramidal neurons in the CA1 hippocampus. Methods Thirty-six sprague dawley rats were divided into 3 groups ： experimental group （ n = 15 ）, ischemic group （ n = 15 ） and control group （ n = 6 ）. Three samples from five time points （6 h, 12 h, 24 h, 48 h and 72 h after surgical manipulation）were collected for the experimental and ischemie groups, while other six animals were untreated and used as controls. The models with middle cerebral artery occlusion （MCAO）were obtained by thread blocking and the models with cerebral ischemic tolerance （IT）were obtained by LIP pretreatment. Neurological severity score（ NSS）, histopathological change, number of inflammatory cells infiltrated and living neuronal cells were determined to evaluate the severity of cerebral ischemic injury. Results There was no significant difference in NSS between experimental and ischemic groups. In contrast, compared with other groups, cerebral pathological change in ischemic group was the most distinct, and significantly more infiltrated inflammatory cells and apoptotic neuronal cells were also observed in the samples collected 24 h, 48 h, and 72 h after surgical manipulation （ P 〈 0. 05）. Conclusions LIP pretreatment could induce ischemic tolerance,probably by providing anti-inflammatory effects and attenuating apoptosis of hippocampal neuronal cells. Therefore, LIP pretreatment could protect brain from infarction after isehemic injury.