酸敏感离子通道2a对缺血预处理诱导大鼠海马缺血耐受的作用

目的探讨脑缺血时的组织病理学变化及酸敏感离子通道2a（ASIC2a）在缺血预处理诱导的脑缺血模型耐受中的作用。方法取成年雄性SD大鼠160只，随机分为假手术组、预缺血组、缺血组、缺血预处理组共4组。行焦油紫染色观察各组大鼠海马CAI区存活神经元密度，TUNEL染色观察大鼠海马CA1区神经元凋亡情况，RT—PCR和Western blotting检测ASIC2a在大鼠海马CAl区mRNA和蛋白表达情况。结果缺血预处理能够显著减少大鼠海马CA1区锥体神经元的死亡和凋亡，PC＋Isch组和Isch组相比具有显著性差异（P〈0．01）。全脑缺血能够上调ASIC2a在大鼠海马CA1区mRNA和蛋白表达，在24h达到高峰，而缺血预处理进一步上调ASIC2a表达，呈进行性上升，在24h和72h时相点，PC＋Isch组和Isch组相比具有显著性差异（P〈0．01）。结论在脑缺血耐受中，缺血预处理对第二次致死性缺血表现出保护作用。在这个过程中，大鼠海马CA1区ASIC2a基因和蛋白表达上调发挥了重要的保护作用。

Ischemic tolerance of ischemic preconditioning on global brain ischemia through up-regulation of acid-sensing ion channel 2a

Objective To investigate the neuroprotective and ischemic tolerance of ischemic preconditioning on global brain ischemia through up-regulation of acid-sensing ion channel 2a（ ASIC2a ）. Methods One hundred and sixty healthly adult male SD rats were randomly divided into 4 groups,i, e. sham group,pre-ischemic group, ischemic group and ischemic preonditiming group. Violet staining was applied to detect neuronal death while the TUNNEL staining was to neuronal apoptosis. RT-PCR and Western Blotting were applied to quantitative detection of ASIC2a mRNA and protein expression in the different groups at different time points in rat hippocampus CA1 region. Results The violet and TUNNEL staining showed the ischemic preconditioning could significantly decreased the death and apoptosis of neuronal cells in CAI region. At six hours after global cerebral ischemia, ASIC2a mRNA began to increase in Isch group which reach to the peak at 24 hours after ischemia. The amount of ASIC2a mRNA and protein were 1.6 times of the Sham group （P 〈 0. 05 ）. Then the expression of ASIC2a mRNA and protein expression declined gradually. However, in ischemic preconditioning hippocampus ASIC2a mRNA and protein increased over time, and even in the 72 hours after ischemia we were able to detect the significantly higher ASIC2a mRNA and protein expression. Conclusions Isehemic preconditioning can significantly increase the mRNA and protein expression of ASIC2a. Therefore, ASIC2a gene and protein may play an important role in ischemic preconditioning-induced ischemic tolerance.