酸敏感离子通道阻断剂对大鼠脑缺血/再灌注的保护效应观察

Protective effects of ASICs blocker on cerebral ischemia/reperfusion in rats

目的:探讨酸敏感离子通道(ASICs)阻断剂阿米洛利(amiloride)对大鼠脑缺血氧化应激性损伤的影响。方法:参照Zea Longa线栓法建立SD大鼠脑局灶性缺血/再灌注(I/R)模型。将32只大鼠随机分为4组,即假手术组、缺血/再灌注(I/R)模型组a、milorideⅠ组和amilorideⅡ组,每组8只。分别于局灶性脑缺血2 h再灌注24 h时间点取冰冻脑片一张进行组织细胞HE染色,其余脑组织制作匀浆,采用生化试剂测定其组织中髓过氧化物酶(MPO)和一氧化氮(NO)的含量。结果:I/R模型组MPO和NO的含量均高于amilorideⅠ组和amilorideⅡ组(P<0.05),amilorideⅠ组高于amilorideⅡ组(P<0.05)。结论:ASICs通道阻断剂amiloride通过抑制脑缺血氧化应激而发挥神经保护作用,其作用机制可能主要为amiloride阻断ASICs通道而抑制Ca2+超载。amiloride药理作用具有剂量-效应关系。

Objective： To investigate the effects of acid sensing ion channels （ASICs） blocker on injury of ischemic cerebral oxidative stress in rats. Methods： The model of focal cerebral ischemia/reperfusion （I/R） in Sprague-Dawley （SD） rats was established with sutured-occluded method invented by Zea Longa. Thirty-two SD rats were randomly divided into four groups including sham operated, I/R model, amiloride Ⅰ and amiloride Ⅱgroup, and each group were eight rats. The rats were randomly taken for HE tissue stain from freezing brain slices and determination to contents of MPO and NO from the other brain tissue homogenized by biochemical reagents at twenty-four hours reperfusion after two hours focal brain ischemia. Results： Compared with I/R model group, the contents of MPO and NO were significantly higher in amiloride Ⅰ and amiloride Ⅱ group （P 〈0.05）, and the amiloride Ⅰ group was higher than amiloride Ⅱ （P 0.05）. Conclusion： ASICs blocker amiloride could have neuroprotective effects by inhibiting oxidative stress in ischemic injury and its mechanisms of neuroprotection was chiefly because amiloride blocks ASICs that results in alleviating Ca^2＋ overloaded. Amiloride was of dose-effect relationship.