甲基强的松龙对深低温停循环大鼠脑保护作用的研究

Methylprednisolone on the cerebral protection of the rats after deep hypothermic circulatory arrest

目的观察甲基强的松龙(MP)对深低温停循环(DHCA)大鼠脑N-甲基-D-天门冬氨酸受体R1(NMDAR1)表达的影响,探讨MP对DHCA大鼠脑保护作用的机制。方法制作大鼠DHCA模型。雄性SD大鼠175只,随机分为假手术组、DHCA模型组和MP处理组。观察DHCA60 min,再灌注2、6、12 h及1、2、3、7 d时NMDAR1蛋白表达的变化以及脑组织超微结构变化。结果免疫组化结果显示,DHCA模型组和MP处理组大鼠NMDAR1蛋白表达均升高,于1 d到达高峰,后逐渐降低,于再灌注7 d恢复至正常水平。MP处理组大鼠再灌注后2、6、12 h,1、2 d5个时间点NMDAR1表达明显低于模型组(P<0.01)。脑组织超微结构观察发现MP能抑制DHCA脑细胞凋亡。结论MP对DHCA大鼠脑组织具有保护作用,其作用机制之一可能是与抑制NMDAR1蛋白表达有关。

Objective To observe the effect of methylprednisolone （MP） on the expression of N-methyl-D-aspartate receptor 1 （ NMDAR1 ） protein following a period of deep hypothermic circulatory arrest （DHCA） in rats. Methods Using Spragne-Dawley rat model of DHCA, 175 SD rats were randomly divided into three groups： sham group ; MP group and model group. After separation from DHCA, rats were killed at 2 h ,4 h, 12 h, 1 d,2 d,3 d and 1 week, the expressions of NMDAR1 protein were detected by immunohistochemistry. Results The expressions of NMDAR1 protein was increased at 2 h after separation from DHCA, reached the peak at 24 h, and gradually come back to normal level at 7 d in MP group and model group. However, preconditioning with MP resulted in a significant reduction in the expressions of NMDAR1 at 2 h,6 h, 12 h, 1 d and 2 d after separation from DHCA comparing with model group （P 〈 0.01 ）. MP could inhibit brain cell apoptosis of the rats after DH- CA. Conclusion MP has a protective effect on the brain of the rat after DHCA. The protective mechanism might be involved with inhibiting NMDA receptor 1 protein expression.