酸敏感离子通道1a对全脑缺血再灌注损伤大鼠神经元凋亡的影响及其可能机制  

Effect of acid-sensing ion channel 1a on neuronal apoptosis of rats with global brain ischemia reperfusion injury and its possible mechanism

作　　者：王梅 许志斌 WANG Mei;XU Zhibin(Department of Anesthesiology,Jiangsu Taizhou People's Hospital,Taizhou 225300,Jiangsu,China;Department of Urology,Jiangsu Taizhou People's Hospital,Taizhou 225300,Jiangsu,China)

机构地区：[1]泰州市人民医院麻醉科,江苏省泰州市225300 [2]泰州市人民医院泌尿外科,江苏省泰州市225300

出　　处：《广西医学》2023年第15期1849-1855,共7页Guangxi Medical Journal

基　　金：泰州市人民医院院级课题(ZL202037)。

摘　　要：目的探讨酸敏感离子通道1a(ASIC1a)对全脑缺血再灌注损伤大鼠海马神经元凋亡的影响及其相关机制。方法将180只雄性SD大鼠随机分为假手术组、模型组、ASIC1a抑制剂组[狼蛛毒素1(PcTx1)组],每组60只。对模型组、PcTx1组大鼠采用四血管阻断法建立全脑缺血再灌注损伤模型,并于再灌注后30 min分别从侧脑室注射无菌无酶PBS和PcTx1;在假手术组中仅分离并暴露大鼠的双侧椎动脉及颈总动脉,不凝断椎动脉及夹闭双侧颈总动脉,再灌注后30 min从侧脑室注射无菌无酶PBS。在再灌注后2 h、6 h、12 h、24 h、48 h,检测各组大鼠海马细胞凋亡率,观察海马CA1区神经元形态学变化,分析海马CA1及CA3区的凋亡指数、磷酸化细胞外信号调节激酶(ERK)1/2的表达水平。结果(1)在再灌注后各时间点,假手术组、PcTx1组、模型组海马细胞凋亡率依次升高(P<0.05)。(2)HE染色结果显示,在再灌注后各时间点,模型组海马CA1区锥体细胞结构被破坏,排列紊乱松散,胞核皱缩,可见凋亡小体,而PcTx1组海马CA1区锥体细胞形态较模型组改善。(3)在再灌注后各时间点,假手术组、PcTx1组、模型组CA1和CA3区的凋亡指数依次升高(P<0.05)。(4)在再灌注后2 h、6 h、12 h、24 h,假手术组、模型组、PcTx1组大鼠海马CA1区的磷酸化ERK1/2表达水平依次升高;在再灌注后48 h,PcTx1组大鼠海马CA1区的磷酸化ERK1/2表达水平亦高于其他两组(P<0.05)。再灌注后2 h、6 h,假手术组、模型组、PcTx1组大鼠海马CA3区的磷酸化ERK1/2表达水平依次升高;在再灌注后12 h,模型组、PcTx1组的磷酸化ERK1/2表达水平高于假手术组(P<0.05)。结论ASIC1a可能参与全脑缺血再灌注损伤大鼠海马神经元凋亡的发生,其特异性阻滞剂PcTx1可减轻神经元细胞凋亡,作用机制可能与促进ERK1/2磷酸化有关。Objective To explore the effect of acid-sensing ion channel 1a(ASIC1a)on neuronal apoptosis of rats with global brain ischemia reperfusion injury and its possible mechanism.Methods A total of 180 SD male rats were randomly divided into sham operation group,model group,ASIC1a inhibitor group(psalmotoxin 1[PcTx1]group),with 60 rats in each group.The global brain ischemia reperfusion injury model was established on rats of the model and PcTx1 groups by using four-vessel blockade method,and then the intra-lateral ventricle injection of sterile and enzyme-free PBS and PcTx1 was performed after 30 minutes of reperfusion,respectively;moreover,in the sham operation group,only bilateral vertebral arteries and common carotid artery of rats were isolated and exposed,while vertebral artery was not congealed,and common carotid artery was not clipped,after 30 minutes of reperfusion,the intra-lateral ventricle injection of sterile and enzyme-free PBS was performed.The apoptotic rate of hippocampus cells in various groups was detected after 2,6,12,24,and 48 hours of reperfusion,and morphological changes of neurons in hippocampus CA1 area were observed,and the apoptotic index,phosphorylated extracellular signal-regulated kinase(ERK)1/2 expression in hippocampus CA1 and CA3 areas were analyzed.Results(1)At various time points after reperfusion,the apoptotic rates of hippocampus cells in the sham operation group,the PcTx1 group,and the model group were elevated successively(P<0.05).(2)The results of HE staining revealed that at various time points after reperfusion,pyramidal cells in hippocampus CA1 area of the model group presented as structural disruption,disordered and loose arrangement,nucleus retraction,and formation of apoptotic bodies,whereas pyramidal cell morphology in hippocampus CA1 area of the PcTx1 group was improved as compared with the model group.(3)At various time points after reperfusion,the apoptotic index in hippocampus CA1 and CA3 areas of the sham operation group,the PcTx1 group,and the model group was elevate

关 键 词：全脑缺血再灌注损伤 酸敏感离子通道1a 海马 凋亡 细胞外信号调节激酶1/2 狼蛛毒素1 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R91[医药卫生—临床医学]