内源性组胺在小鼠缺血预处理诱导的脑缺血耐受中的作用

目的:利用组氨酸脱羧酶敲除(HDC-KO)小鼠,研究组胺是否参与缺血预处理诱导的脑缺血耐受的形成.方法:分别将野生型(WT)小鼠双侧颈总动脉夹闭(BCCAO)6、10、14 min,再灌注48 h后,再持续BCCAO进行永久性前脑缺血,观察其缺血耐受时间.部分小鼠取脑、冰冻切片、进行甲苯胺蓝染色,观察神经元损伤情况.比较BCCAO 预处理10 min对WT和HDC-KO小鼠永久性前脑缺血耐受时间的影响.测定WT小鼠再灌30 min、5 h、48 h脑内组胺含量.结果:缺血预处理各时间点均可延长WT小鼠在永久性前脑缺血后的存活时间,其中预处理10 min有显著性差异,并且未引起海马和纹状体神经元的损伤.但预处理10 min不能诱导HDC-KO小鼠脑缺血耐受的形成.WT小鼠预处理10 min再灌30min、48 h时脑内组胺含量升高,但再灌5 h时与对照组相比无明显变化.结论:内源性组胺可能参与缺血预处理诱导的脑缺血耐受的形成,其作用机制有待进一步深入研究.

Effect of endogenous histamine on ischemic preconditioning induced cerebral ischemic tolerance

Objective: To investigate the effect of endogenous histamine on ischemic preconditioning induced cerebral ischemic tolerance in rats. Methods: Wild-type (WT) mice and histidine decarboxylase knock-out (HDC-KO) mice were preconditioned by bilateral carotid artery occlusion (BCCAO) for 6,10,or 14 min and reperfused for 48 h,then subjected to permanent BCCAO and the survival time of WT and HDC-KO mice subjected to permanent BCCAO was observed.Histamine levels in the hypothalamus,hippocampus,striatum and cortex at 0.5 h,5 h or 48 h after 10 min BCCAO were determined with high-performance liquid chromatography. Results: Ten minutes ischemic preconditioning significantly prolonged the survival time of WT mice subjected to permanent BCCAO.However,in HDC-KO mice,the ischemic tolerance was not induced with 10 min preconditioning.The histamine levels at 0.5 h or 48 h increased after 10 min preconditioning,but not at 5 h. Conclusion: Endogenous histamine in brain may be an essential mediator in ischemic preconditioning induced cerebral ischemic tolerance.