鼠脑缺血再灌注损伤炎症反应及环磷酰胺影响

Effect of cyclophosphamide on inflammatory reaction of cerebral ischemia reperfusion injury in rats

目的探讨脑缺血再灌注不同缺血区域炎症反应特点及环磷酰胺影响。方法将大鼠随机分为假手术组、对照组、环磷酰胺预处理组,建立局灶性脑缺血再灌注模型。用免疫组化法和生化法观察额顶部皮质和基底节区P-选择素表达、髓过氧化物酶(MPO)活性变化;并进行TTC染色和HE染色。结果(1)再灌注3h缺血侧额顶部皮质和基底节区出现P-选择素表达,12h达高峰。环磷酰胺预处理组和对照组相比较,差异无显著性(P>0.05)。(2)再灌注12h以后MPO活性明显升高。基底节区的MPO活性在再灌注48h达到高峰后下降。额顶部皮质MPO活性在再灌注24h达到高峰后至96h仍维持较高水平。和对照组相比较,环磷酰胺预处理组MPO活性升高受抑制(P<0.05)。(3)环磷酰胺预处理可显著缩小脑梗死体积(P<0.05)。结论(1)脑缺血再灌注损伤存在主动性炎症反应,额顶部皮质比基底节区的炎症反应更持久和剧烈。(2)环磷酰胺减少缺血侧中性粒细胞浸润数量,具有神经保护作用,但不直接影响P-选择素的表达。

Objective To study the inflammatory reaction characters in distinct ischemic territory and the effect of cyclophosphamide on focal cerebral ischemia-reperfusion injury in rats. Methods In this experiment,rats were randomly divided into 3 groups,which were sham operated group,saline control group and cyclophosphamide pretreament group. The focal middle cerebral artery occlusion(MCAO) model was made. After different durations of reperfusion following MCAO,we investigated the expression of P-selectin using immunohistochemistry and investigated the MPO activity in the frontal and parietal cortex and basal ganglia. HE staining and TTC staining was also investigated. Results (1) Expression of P-selectin slightly increased at 3h and peaked at 12h in the frontal and parietal cortex and basal ganglia. There had no significant statistical difference between pretreament group and control group(P> 0.05 ). (2)MPO activity was started to increased significantly after 12h of reperfusion. In ischemic basal ganglia,MPO activity peaked at 48h,then gradually descended. In the frontal and parietal cortex,MPO activity peaked at 24h,and remained elevated by 96h. Compared with control group,the increase of MPO activity was completely inhibited after reperfusion in cyclophosphamide pretreament group(P< 0.05 ). (3) Compared with control group,Cyclophosphamide reduced cerebral infarction volume (P< 0.05 ). Conclusion (1) There is inflammation reaction after cerebral ischemia-reperfusion injury,which is more persistent and intensive in ischemic frontal and parietal cortex than in basal ganglia. (2)Cyclophosphamide may reduce cerebral ischemia-reperfusion injure by decreasing neutrophils infiltration,while it may have no directly relation to the expression of P-selectin.