亚低温对大鼠局灶脑缺血皮质神经元p53蛋白表达及凋亡的影响

Effects of Mild Hypothermia on the Expression of p53 and Neuron Apoptosis in Brain Cortex after Reperfusion of Focal Cerebral Ischemia in Rats

目的观察亚低温对大鼠局灶脑缺血再灌注后皮质神经元p53蛋白表达及凋亡的影响,探讨亚低温脑保护机制。方法采用改良法建立成年SD大鼠大脑中动脉闭塞(MCAO)局灶脑缺血再灌注模型,缺血时间2h。将实验大鼠随机分成常温组和亚低温组,2组再随机分成2%氯化2,3,5-三苯四氮唑(TTC)组和凋亡组2个亚组,各亚组再分成假手术组,再灌注6,24,72 h组。TTC染色检测脑梗死体积、TUNEL染色观察细胞凋亡、免疫组织化学染色观察p53蛋白的表达水平。结果与常温组相比,亚低温组大鼠脑梗死体积小、缺血灶周围皮质神经细胞凋亡少、p53蛋白表达下降。结论亚低温神经保护机制涉及下调p53蛋白表达,从而抑制神经元凋亡,缩小大鼠脑梗死体积,减轻神经功能缺损体征。

Objective To observe the effects of mild hypothermia on the expression of p53 and neuron apoptosis, for exploring the neuroprotective mechanisms of mild hypothermia. Methods The modified transient focal cerebral ischemic models of male adult SD rats were established by occlusion of middle cerebral artery for 2 hours. The model rats were randomizely divided into two groups, normothermic ischemic group and hypothermic ischemic group. Infarction volume was measured with triphenyl-tetrazolium chloride（TTC） staining. Apoptosis after focal ischemia was examined with TUNEL staining. The expressions of p53 were measured with immunohistochemical staining. Results Compared to normothermic group, the infarct volume and the quantity of apoptotic neurons was significantly decreased in mild hypothermic group than the normothermic ischemic group. The quantity of p53 postive neuron in mild hypothermic group was （27.84 ±1.59） in 72 h, compared with norrnotherrnic ishemic group（42.69±1.48, P〈0.01） Conclusion Neuroprotective mechanism of mild hypothermia possibly includes decreasing the expression of p53 protein, which attenuated the neuronal apoptosis, and then reduced infarct volume.