依达拉奉对心肺复苏后脑水通道蛋白-4表达的影响

目的 探讨大鼠心肺复苏后脑水通道蛋白-4(AQP4)表达与脑水肿动态变化的关系,评价依达拉奉的干预作用.方法 72只雄性SD大鼠随机分为4组:正常对照组(A组,6只),假手术组(B组,6只),复苏组(C组,按ROSC后1 h,6 h、12 h、24 h、72 h各时点分5亚组,各6只),依达拉奉处理组(D组,亚组同C组),复苏即刻予以依达拉奉干预.分别测定脑组织含水量,免疫组化法检测其AQP4蛋白表达,行神经功能缺损评分(neurodeficit score,NDS)及脑组织病理形态学观察.结果 C组大鼠ROSC后脑组织含水量呈上升趋势,24 h达高峰,各时点均高于B组(P<0.01).AQP4表达呈现与脑含水量同样趋势改变,积分光密度(iOD)、显色面积比(△S)增加(P<0.01),相关性分析表明iOD(r=0.858,P<0.01)、AS(r=0.870,P<0.01)与脑组织含水量呈正相关.与C组相比,依达拉奉干预处理后脑组织含水量明显下降(P<0.05);AQP4蛋白iOD、△S显著下调(P<0.01);病理学损伤程度减轻,NDS评分显著提高(P<0.05).结论 大鼠心肺复苏后脑AQP4表达上调,与脑水肿变化正相关,AQP4可能参与心肺复苏后脑水肿形成.依达拉奉可抑制AQP4表达,减轻大鼠心肺复苏后脑水肿,具有脑保护作用

The intervention effects of edaravone on aquaporin-4 expression in the rat brain following cardiopulmonary resuscitation

Objective To investigate the relationship between aquaporin-4 (AQP4) expression level inbrain and dynamic change of brain edema in rats after cardiopulmonary resuscitation (CPR), and to evaluate the in-tervention effects of Edaravone. Method Totally 72 Sprague-Dawley male rats were randomly divided into fourgroups:normal group (n = 6, group A) ,shame-operated group ( n = 6, group B), CPR group including 1 hour,6 hours, 12 hours, 24 hours, and 72 hours after ROSC (5 sub-groups, n = 6for each,group C) ,edaravone-treat-ed group with the same time points as CPR groups(5 sub-groups, n = 6for each,group D). Asphyxia cardiac ar-rest with CPR model was used in group C and group D. Edaravone at a dose of 3.0 mg/kg was given intravenouslyand the same dose of edaravone was administered subcutaneously to the rats of group D after CPR. Anaesthosia,vascular cannulation and endotracheal intubation were pedormed in rats without asphyxia and CPR in group B. Ateach interval, the brain water content was calculated. The AQP4 expression level in brain tissue was determinedusing immunohistocbemical staining. Neurodeficit scores were assessed and pathological change was observed, Re-sults The brain water content in rats of group C increased obviously along with the prolongation of time followingROSC,and reached its peak at ROSC 24h,which was much higher than that of group B (P<0.01). Meanwhile,AQP4 expression in brain had a trend towards increasing and the integral optical density(iOD) and coloratian arearatio(△S) in group C were significantly increased compared with group B ( P<0.01). The trend of changes wasnearly the same as that of the brain water content. The correlation analysis demonstrated that AQP4 expression levelsuch as iOD (r=0.858, P < 0.01 ) and △S ( r = 0.870, P < 0.01 ) were correlated with the brain watercontents apparently. Compared with group C, the brain water content was decreased obviously (P<0.05), iODand △S was down-regulated at the same lime (P<0.01) in group D. The neurodeficit scores increased (P <0.05) and pathological damage was dramatieaUy ameliorated. Conclusions AQP4 expression increased greatly inbrain after CPR and the relationship between AQP4 and brain edema was positively correlated. AQP4 may play arole in the formation of brain edema following CPR. Edaravone could attenuated brain edema after CPR in rats byway of inhibiting the expression of AQP4. It had neuroprotective effect.