浅低温对大鼠全脑缺血再灌注酸敏感离子通道1a和2a表达的影响
천저온대대서전뇌결혈재관주산민감리자통도1a화2a표체적영향
Effect of mild hypothermia on the expression of acid-sensing ion channels 1a and 2a following global cerebral ischemia-reperfusion in rats
  • 万方数据
    中华医学杂志 중화의학잡지
    National Medical Journal of China
    2013年 7期 546-549 ,共4页

    高玮%曾秋婷%程慧娴%崔耀梅%李茜%孙茜%段满林%徐建国

    고위%증추정%정혜한%최요매%리천%손천%단만림%서건국

    低温%脑缺血%再灌注损伤%酸敏感离子通道 低溫%腦缺血%再灌註損傷%痠敏感離子通道
    저온%뇌결혈%재관주손상%산민감리자통도
    Hypothermia%Brain ischemia%Reperfusion injury%Acid-sensing Ion Channels
    目的 探讨浅低温对大鼠全脑缺血再灌注后酸敏感离子通道1a(ASIC1a)和2a(ASIC2a)的影响及在脑复苏作用中的潜在机制.方法 95只雄性SD大鼠随机数字表分为以下5组(n=19):假手术组(Ⅰ)、模型组(Ⅱ)、浅低温组(Ⅲ)、PcTX1组(Ⅳ)、浅低温+PcTX1组(Ⅴ).四血管阻塞法建立大鼠全脑缺血再灌注损伤模型,缺血15 min,再灌注即刻Ⅳ组和Ⅴ组侧脑室注射500 ng/ml PcTX1 6μl,其余组侧脑室注射等容量生理盐水.同时Ⅲ组和Ⅴ组于再灌注15 min内将直肠温度降至32～ 33℃,并维持6h,其余组维持直肠温度36～37℃.测定再灌注6h及24 h海马ASIC1a和ASIC2a蛋白水平、再灌注24 h海马ASIC1a和ASIC2a mRNA表达水平；观察再灌注24h海马CA1区病理改变；以及测定再灌注72 h大鼠脑含水量.结果 与Ⅰ组比,其余各组ASIC1a mRNA和蛋白的表达差异无统计学意义(P＞0.05)；与Ⅰ组比,其余各组ASIC2a mRNA和蛋白的表达均增高(P＜0.05)；与Ⅱ组和Ⅳ组比,Ⅲ组和Ⅴ组ASIC2a mRNA和蛋白的表达增高(P＜0.05)；与再灌注6h相比,再灌注24hⅡ、Ⅲ、Ⅳ和Ⅴ组ASIC2a蛋白表达均增高(P＜0.05)；与Ⅰ组比,Ⅱ、Ⅲ、Ⅳ和Ⅴ组CA1区锥体细胞数均减少(P＜0.01)；与Ⅱ组比,Ⅲ、Ⅳ和Ⅴ组CA1区锥体细胞数均增加(P＜0.01),尤以Ⅴ组效果最明显(P＜0.01)；与Ⅰ组比,Ⅱ、Ⅲ和Ⅳ组脑水含量均增加(P＜0.01)；与Ⅱ组比,Ⅲ、Ⅳ和Ⅴ组脑水含量均降低(P＜0.01),Ⅴ组降低最明显(P＜0.01).结论 浅低温减轻大鼠全脑缺血再灌注损伤可能与ASIC2a mRNA和蛋白表达上调有关,且浅低温联合PcTX1对缺血脑组织的复苏具有协同作用.
    목적 탐토천저온대대서전뇌결혈재관주후산민감리자통도1a(ASIC1a)화2a(ASIC2a)적영향급재뇌복소작용중적잠재궤제.방법 95지웅성SD대서수궤수자표분위이하5조(n=19):가수술조(Ⅰ)、모형조(Ⅱ)、천저온조(Ⅲ)、PcTX1조(Ⅳ)、천저온+PcTX1조(Ⅴ).사혈관조새법건립대서전뇌결혈재관주손상모형,결혈15 min,재관주즉각Ⅳ조화Ⅴ조측뇌실주사500 ng/ml PcTX1 6μl,기여조측뇌실주사등용량생리염수.동시Ⅲ조화Ⅴ조우재관주15 min내장직장온도강지32～ 33℃,병유지6h,기여조유지직장온도36～37℃.측정재관주6h급24 h해마ASIC1a화ASIC2a단백수평、재관주24 h해마ASIC1a화ASIC2a mRNA표체수평；관찰재관주24h해마CA1구병리개변；이급측정재관주72 h대서뇌함수량.결과 여Ⅰ조비,기여각조ASIC1a mRNA화단백적표체차이무통계학의의(P＞0.05)；여Ⅰ조비,기여각조ASIC2a mRNA화단백적표체균증고(P＜0.05)；여Ⅱ조화Ⅳ조비,Ⅲ조화Ⅴ조ASIC2a mRNA화단백적표체증고(P＜0.05)；여재관주6h상비,재관주24hⅡ、Ⅲ、Ⅳ화Ⅴ조ASIC2a단백표체균증고(P＜0.05)；여Ⅰ조비,Ⅱ、Ⅲ、Ⅳ화Ⅴ조CA1구추체세포수균감소(P＜0.01)；여Ⅱ조비,Ⅲ、Ⅳ화Ⅴ조CA1구추체세포수균증가(P＜0.01),우이Ⅴ조효과최명현(P＜0.01)；여Ⅰ조비,Ⅱ、Ⅲ화Ⅳ조뇌수함량균증가(P＜0.01)；여Ⅱ조비,Ⅲ、Ⅳ화Ⅴ조뇌수함량균강저(P＜0.01),Ⅴ조강저최명현(P＜0.01).결론 천저온감경대서전뇌결혈재관주손상가능여ASIC2a mRNA화단백표체상조유관,차천저온연합PcTX1대결혈뇌조직적복소구유협동작용.
    Objective To investigate the effects of mild hypothermia on the expression of ASIC1a and ASIC2a in the rat hippocampus following global cerebral ischemia-reperfusion,so as to speculate the underlying mechanisms of neuroresuscitation.Methods Ninety five male SD rats were randomly divided into five groups (n =19):sham operation group(Ⅰ),model group(Ⅱ),mild hypothermia group(Ⅲ),PcTX1 group(Ⅳ),mild hypothermia combined PcTX1 group(Ⅴ).Transient (15 min) global cerebral ischemia was induced by the four-vessel occlusion.PcTX1 (500 ng/ml) 6 μl were injected into lateral cerebral ventricle immediately after reperfusion in group Ⅳ and Ⅴ,while the equal volume of normal saline was injected into lateral cerebral ventricle immediately after reperfusion in the other three groups.At the same time,mild hypothermia after reperfusion was performed and lasted for 6 hours in group Ⅲ and Ⅴ,the rectal temperature was reduced to 32-33 ℃ within 15 min,while it was maintained at 36-37 ℃ by lamp in other three groups.Determination the expression of ASIC1a and ASIC2a protein at 6 h and 24 h of reperfusion,and the expression of ASIC1 a and ASIC2a mRNA at 24 h of reperfusion.Observe the pathomorphological changes of hippocampal CA1 neurons at 24 h of reperfusion.Detect the brain water content at 72 h of reperfusion.Results The difference in the expression of ASIC1a mRNA and protein among the groups was not changedsignificantly (P ＞ 0.05).Compared with group Ⅰ,the expression of ASIC2a mRNA and ASIC2a protein was up-regulated in other groups (P ＜ 0.05).It was significantly higher in group Ⅲ and Ⅴ than in group Ⅱ and Ⅳ (P ＜ 0.05).Compared to 6 h of reperfusion,the expression of ASIC2a protein was higher in group Ⅱ,Ⅲ,Ⅳ and Ⅴ respectively after 24 h of reperfusion.Compared to group Ⅰ,the number of pyramidal cells in CA1 region of hippocampus in group Ⅱ,Ⅲ,Ⅳ and Ⅴ were decreased at 24 h of reperfusion (P ＜0.01).Compared to group Ⅱ,the number of pyramidal cells in CA1 region of hippocampus in group Ⅲ,Ⅳ and Ⅴ were increased at 24 h of reperfusion (P ＜ 0.01) ; and compared to group Ⅲ and Ⅳ,the number of pyramidal cells at 24 h of reperfusion in group Ⅴ was significantly higher (P ＜ 0.01).Compared to group Ⅰ,the content of brain water in Ⅱ,Ⅲ and Ⅳ group were increased at 72 h of reperfusion (P ＜0.01).Compared to group Ⅱ,the content of brain water in group Ⅲ,Ⅳ and Ⅴ were decreased at 72 h of reperfusion (P ＜ 0.01).Giving mild hypothermia or PcTX1 could alleviant the damage in CA1 region of hippocampus,with the best effect in group Ⅴ,which administers PcTX1 combined mild hypothermia.Conclusion Mild hypothermia attenuates global cerebral ischemia-reperfusion of rat,which may up-regulate the expression of ASIC2a mRNA and protein.Mild hypothermia combined by PcTX1 could induce neuroresuscitation.
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