二氮嗪对深低温脑缺血再灌注大鼠脑组织NR1表达的影响

目的 探讨二氮嗪对深低温缺血再灌注大鼠的脑保护作用及其机制。方法 采用双侧颈总动脉阻断法制作深低温缺血再灌注大鼠模型,将306只SD大鼠随机分成3组：假手术组、二氮嗪组和模型组。分别在缺血1 h后再灌注2、6、12 h及1、2、3、7 d断头取脑,对脑组织行含水量检测,并采用免疫组织化学技术检测脑组织NR1表达情况。结果 假手术组脑组织含水量明显低于二氮嗪组和模型组,二氮嗪组低于模型组,模型组和二氮嗪组脑组织含水量在12 h开始升高、1d达高峰、3 d基本恢复正常,模型组和二氮嗪组NR1均在2 h开始升高、1 d达到高峰、7 d后基本达到正常水平,但二氮嗪组NR1表达水平在2、6、12 h及1、2 d明显低于模型组,且两组NR1表达水平均高于假手术组。结论 二氮嗪预处理对深低温缺血再灌注大鼠具有脑保护作用,其作用机制可能是通过下调脑组织NR1的表达来实现。

Influence of diazoxide on the expression of NR1 after deep hypothermic brain ischemia/reperfusion in rats

Objective To observe the effect and mechanism of diazoxide on the brain protection following a period of deep hypothermic brain ischemia/reperfusion injury in rats.Methods The deep hypothermic brain ischemia/reperfusion models of rats were performed by blocking up double arteria carotis communis.Three hundreds and six SD rats were randomly divided into three groups:sham group,diazoxide group and model group.After 1 h of brain ischemia,rats were killed at 2,6,12 h and 1,2,3,7 d of reperfusion.Brain moisture capacity was measured,while the expressions of N-methyl-D-aspartate receptor 1(NR1)was detected by immunohistochemistry.Results Brain moisture capacity of sham group was obviously lower than diazoxide group and model group whereas diazoxide group was lower than model group.It stepped up at 12 h,reached peak at 24 h,and gradually came back to normal level at 3 d in diazoxide group and model group.The expressions of NR1 was increased at 2 h,reached peak at 24 h,and gradually returned to normal level at 7 d in diazoxide group and model group.However,preconditioning with diazoxide resulted in a significant reduction in the expressions of NR1 at 2,6,12 h and 1,2 d comparing to model group.The expressions of NR1 of the both group were increased than sham group.Conclusion Preconditioning with diazoxide on deep hypothermic brain ischemia/reperfusion rats have the effect of brain protection.The mechanism of brain protection may result from down regulation of the expression of NR1.