酸敏感离子通道1a在大鼠全脑缺血再灌注损伤中的作用

Role of acid-sensing ion channel la in global cerebral ischemia-reperfnsion injury in rats

目的探讨酸敏感离子通道1a（ASIC1a）在大鼠全脑缺血再灌注损伤中的作用。方法成年雄性SD大鼠40只，体重250～300g，采用随机数字表法，将大鼠随机分为4组（n=10）：假手术组（S组）、全脑缺血再灌注组（I／R组）、ASIC1a特异性阻断剂PcTX1组（P组）和溶剂对照组（SC组）。采用改良的Pulsinelli四血管阻断法制备大鼠全脑缺血再灌注损伤模型。P组和SC组于再灌注即刻分别经侧脑室注射PcTX1（500ng／m1）6出和双蒸水6脚。再灌注24h时处死大鼠，取海马组织，采用Westernblot法测定Caspase-3的表达，采用免疫组织化学法检测海马CA1区Bc1-2、Bax的表达水平，并观察海马病理学结果。结果与S组比较，I／R组、P组和SC组海马Caspase-3、Bcl-2和Bax表达上调（P〈0．05）；与I／R组比较，P组海马Caspase-3和Bax表达下调，Bcl-2表达上调（P〈0．05），XC组差异无统计学意义（P〉0．05）。P组海马病理学损伤较I／R组减轻。结论ASIC1a激活后可能通过上调脑组织Caspase-3和Bax的表达，下调Bcl-2的表达，诱发细胞凋亡，从而导致大鼠全脑缺血再灌注损伤。

Objective To investigate the role of acid-sensing ion channel 1 a（ ASICI a） in global cerebral ischemia-reperfusion injury in rats. Methods Forty male SD rats weighing 250-300 g were randomly divided into 4 groups （n = 10 each） ： sham operation group （group S）, cerebral ischemia-reperfusion group （group I/R）, solvent control group （group SC） and group PcTX1 （a ASICla blocker, group P）. Global cerebral ischemia-reperfusion was induced by four-vessel occlusion. PcTXI（500 ng/ml）6 μl or solvent 6 μl was injected into the crerbral ventricular at the begining of reperfusion in groups P and SC respectively. The rats were sacrificed at 24 h of reperfusion, and then the hippocampi were removed for determination of Caspase-3, Bcl-2 and Bax protein expression and microscopic examination. Results Compared with group S, the expression of Caspase-3, Bcl-2 and Bax protein was up-regulated in groups I/R, SC and P （P 〈 0.05） . Compared with group I/R, the expression of Caspase-3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in group P （P 〈 0.05）. There was no significant difference in Caspase-3, Bcl-2 and Bax protein expression between groups I/R and SC （P 〉 0.05）. The histopathologic damage was ameliorated in group P as compared with group I/R. Conclusion ASICla can induce global cerebral ischemia-reperfusion injury in rats by up-regulating Caspase-3 and Bax expression, and down-regulating Bcl-2 expression and inducing apoptosis.