内源性组胺减轻小鼠前脑缺血再灌注后期脑损伤*

 目的： 研究内源性组胺在前脑缺血再灌注后期的神经保护作用。方法: 将野生型（WT）小鼠和组氨酸脱羧酶基因敲除（HDC-KO）小鼠各随机分为对照组和缺血组，缺血组小鼠双侧颈总动脉夹闭30 min以建立前脑缺血模型，比较再灌后WT和HDC-KO小鼠的体重变化和死亡率，并在再灌14 d时对各组存活小鼠进行条件性恐惧学习记忆测试，再灌3 d及15 d时，对各组小鼠取脑,制作冰冻切片,进行甲苯胺蓝染色，观察海马CA1区神经元损伤情况。结果: 再灌1 d后，WT和HDC-KO小鼠均出现体重下降，再灌4 d、5 d、6 d及7 d后，HDC-KO小鼠的体重恢复程度均显著低于WT小鼠。前脑缺血再灌8~14 d，HDC-KO小鼠的死亡率显著高于WT小鼠（P<0.05）。再灌14 d后，HDC-KO小鼠的背景及线索记忆能力均显著低于WT小鼠（P<0.05）。再灌3 d后，HDC-KO和WT小鼠的海马CA1区神经元密度无显著差异，而再灌15 d后，HDC-KO小鼠海马CA1区神经元密度显著低于WT小鼠（P<0.05）。结论: 内源性组胺可减轻脑缺血再灌注后期的学习记忆能力下降及神经元缺失，但其作用机制有待进一步研究。

Effects of endogenous histamine on transient forebrain ischemia-induced neuronal damage at late phase of reperfusion in mice

AIM: To determine the effect of endogenous histamine on transient forebrain ischemia-induced neuronal injury at the late phase of reperfusion using histidine decarboxylase knockout (HDC-KO) mice. METHODS: Wild-type (WT) and HDC-KO mice were subjected to bilateral common carotid artery occlusion for 30 min followed by 3 d or 15 d of reperfusion. At different time points after reperfusion, the body weight, mortality rate, learning and memory in fear conditioning test and hippocampal CA1 neuronal density were evaluated. RESULTS: At 1 d after reperfusion, the body weight loss was observed in both WT and HDC-KO mice. At 4 d, 5 d, 6 d and 7 d after reperfusion, the increment in the body weight of the HDC-KO mice was significantly smaller than that of the WT mice. During the period between 8 d and 14 d after reperfusion, the mortality rate of the HDC-KO mice was higher than that of the WT mice (P<0.05). At 14 d after reperfusion, the HDC-KO mice exhibited more aggravated deficits in contextual and cue memory compared with the WT mice. Correspondingly, a more severe CA1 neuronal injury in the HDC-KO mice than that in the WT mice was observed at 15 d but not at 3 d after reperfusion (P<0.05). CONCLUSION: Endogenous histamine may attenuate learning/memory deficits and neuronal injury at the late phase of ischemia/reperfusion. However, the involved mechanisms need to be further investigated.