大鼠脑缺血及再灌注损伤的亚低温治疗时间窗研究

The study of therapeutic time window of mild hypothermia in cerebral ischemia and reperfusion injury in rat

目的 研究大鼠脑缺血再灌注损伤的亚低温 (32± 1℃ )治疗时间窗 ,探讨最长脑缺血时间和开始低温时间所能获得的有效脑保护作用。方法 采用改良线栓法制备大鼠大脑中动脉缺血再灌注模型。将72只SD大鼠随机分为 12组 ,缺血后常温组 (分 4个亚组 ) :缺血 4、6、8及 10小时后再灌注亚组 ;缺血后亚低温组 (缺血模型建立后开始亚低温并持续 12小时 ,分 4个亚组 ) :缺血 4、6、8及 10小时后再灌注亚组 ;再灌注期亚低温组 (再灌注后开始亚低温并持续 12小时 ,分 4个亚组 ) :缺血 4、6、8、及 10小时后再灌注亚组。观察脑梗死体积、脑组织水分含量和病理改变。结果 缺血后亚低温能显著减小脑梗死体积 (与对照组比较 ,脑梗死体积减小 92 .2 %～ 6 5 .3% ;再灌注期亚低温组除缺血 10小时后再灌注亚组无统计学意义外 ,其它亚组脑梗死体积减小 6 8.4%～ 36 .79%。结论 结果显示缺血后亚低温的脑保护作用非常显著 ,提示超早期诱导亚低温可能延长溶栓治疗时间窗 ;缺血 4小时后开始诱导亚低温效果较好 ,缺血 8小时后开始诱导亚低温仍有效。

Objective To investigate the therapeutic time window of mild hypothermia in cerebral ischemia and reperfusion injury in rat and to study the maximal ischemic phase and optimal timing of mild hypothermia (32±1℃) in which the significant cerebroprotective effect can be obtained. Methods The seventy two SD rats were divided randomly into twelve groups (each group n =6). Normothermia group included the ischemic 4, 6, 8, 10 h sub groups, intra ischemia and intra reperfusion hypothermia group contained ischemic 4, 6, 8, 10 h sub groups in which the mild hypothermia continued for 12 hours. Intra reperfusion hypothermia group was comprised of ischemic 4, 6, 8, 10 h sub groups and the mild hypothermia last out for 12 hours. The infarct volume, brain water content and pathological changes were observed. Results The infarct volumes were very small in the intra ischemia and intra reperfusion hypothermia group(reduced by 92.2 %～ 65.3 % compared with the nomothemia groups).Those were also decreased by 68.4% ～ 36.79% in the ischemic 4, 6, 8 h sub groups of the intra reperfusion hypothermia group except that there were not statistical significance in the ischemic 10 h sub group compared with those of nomothermia groups. Conclusion This study suggests that the mild hypothermia should have the neuroprotective effect and reduce the infarct volumes significantly in all groups except in the ischemic 10 h sub group of intra reperfusion hypothermia group. The mild hypothermia induced in 4 h may be optimic theratheutic window.