大鼠脑缺血不同时间再灌注脑损伤的实验研究

目的 通过了解大鼠脑缺血不同时间再灌注神经细胞坏死情况，进一步探讨溶栓时间窗问题。方法 应用SD大鼠建立大鼠大脑中动脉局灶脑缺血模型，分脑缺血再灌注组(缺血1／2、1、2、3、4、5、6h再灌注2，4、48、72h)、脑梗死组、永久缺血组及假手术组，于再灌注后24、48、72h处死大鼠取脑，免疫组织化学方法观察细胞间粘附因子1(ICAM-1)表达、TTC测定脑梗死体积。结果 缺血1／2h，再灌注24h时ICAM-1表达开始增加，随着脑缺血时间的延长，ICAM-1表达呈上升趋势；ICAM-1表达高峰的缺血时间为3h。每个缺血时间点内，ICAM-1表达高峰的再灌注时间是48h。缺血1h再灌注可降低ICAM-1表达，减轻脑梗死面积，但缺血3h后再灌注增加ICAM-1的表达且增加脑梗死面积。结论 ICAM-1参与了脑缺血后的炎症反应，促使缺血后继发脑损伤。一般情况下，血管再通应在缺血3h内进行，否则再灌注损伤带来的副面影响将远远大于恢复血流本身。

The reperfusion damage of rat brain after different lengths of cerebral ischemia

Objective To define the thrombolytic therapeutic time window by investigating the neuronal damage after varied lengths of cerebral ischemia/reperfusion in rats. Methods SD rats were divided into groups: sham operation group, permanent ischemia control group and ischemia/reperfusion groups (ischemia for 1/2, 1 , 2, 3, 4, 5 and 6 h; reperfusion for 24, 48 and 72 h). The middle cerebral artery occlusion (MCAO) model was built by inserting filament into the carotid artery. Immunohistochemistry and histological techniques were used to determine expression of ICAM-1 gene, the infarct volume in ischemic brain tissue was measured after TTC staining. Results It was found that ICAM-1 expression started to increase at 1/2 hour of ischemia after 24 hours of reperfusion,and peaked at 3 hours of ischemia. The expression of ICAM after varied length of ischemia reached its peak at 48 hours reperfusion. With reperfusion started after 1 h of ischemia, there would be less expression of ICAM-1 and smaller infarct volume, while after 3 hours of ischemia, the expression of ICAM-1 and infarct volume would be greatly increased. Conclusion ICAM-1 participates in the inflammation reaction and tissue damage after cerebral ischemia. Generally speaking, measures to re-canalize the occluded vessel should be taken within 3 h of ischemia, so to avoid the severe secondary reperfusion injuries overbalancing the benefits of the restored blood supply to the concerned region of the brain.