酸性环境介导皮质神经元损伤及阻断酸敏感离子通道1α的神经保护作用

Cortical neuron injury mediated by acidosis and neuroprotection by blocking acid-sensing ion channel 1α

目的探讨脑梗死模型中酸性环境能否介导皮质神经元损伤及阻断酸敏感离子通道1α(acidsensing ion channels1α,ASIC1α)的神经保护作用。方法制作缺氧细胞模型、脑梗死动物模型,检测ASIC1α阻断剂对乳酸脱氢酸(lactate dehydrogenase,LDH)释放率、大鼠行为学、脑梗死体积以及ASIC1蛋白表达的影响。结果酸性环境可以损伤皮质神经元,加重缺氧对细胞的毒性作用,经侧脑室注射ASIC1α阻断剂可以改善脑梗死大鼠的行为学改变,梗死体积明显减小(P<0.05);随梗死时间延长,缺血半暗带ASIC1表达增加,在缺血后24h表达量较明显。结论酸性环境导致皮质神经元损伤,其损伤机制与缺血后神经元ASIC1α开放以及表达增加有关;阻断ASIC1α具有神经保护作用。

Objective To investigate the cortical neuron injury mediated by acidosis in models of cerebral infarction and neuroprotection by blockade of acid-sensing ion channel 1α. Methods Oxygen deprivate neuron and cerebral infarction rats were used to investigate ASIC1α Blockers effects on Behavioral changes, infarct volume and expression of ASIC1. Results Acidosis injured cortical neurons and enhanced the toxic effects of oxygen glucose deprivation, ASIC1α blockers dramatically reduced the injure. In penumbra areas of ischemia model,expression of ASIC1 increased as ischemia impairment developed, which was increased obviously 24 h after cerebral ischemia. ASIC1α blockers injection improved the abnormal behaviors of ischemia rats and decreased infarct volume （P〈0. 05）. Conclusions Acidosis induces cortical neurons injure,ASIC1 opening and up-regulatian perheps involved in. Blocking ASIC1α plays a neuroprotective role.