α7nAChR激动剂对体外循环致大鼠脑损伤的影响  

Effect of α7nAChR agonists on brain injury induced by cardiopulmonary bypass in rats

作　　者：王梅[1] 孙莹杰[1] 张铁铮[1] 

机构地区：[1]沈阳军区总医院麻醉科,110016

出　　处：《中华麻醉学杂志》2016年第8期930-933,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金面上项目（81471121）

摘　　要：目的 评价α7烟碱型胆碱能受体（α7nAChR）激动剂对体外循环（CPB）致大鼠脑损伤的影响.方法 清洁级成年雄性SD大鼠72只,体重350～ 450 g,采用随机数字表法分为3组（n=24）：假手术组（S组）、CPB组和α7nAChR激动剂PHA568487组（PHA组）.S组不进行CPB,机械通气60 min;CPB组和PHA组行CPB 60 min.CPB前30 min时PHA组腹腔注射PHA568487 0.8mg/kg,CPB组腹腔注射等容量生理盐水.分别于CPB前（T0）、CPB结束即刻（T1）、术后2 h（T2）和术后6 h（T3）时,处死6只大鼠,颈内静脉采血样,采用ELISA法检测血清S100β蛋白、IL-6和TNF-α的浓度,HE染色法观察海马组织病理学改变;TUNEL法测定海马神经元凋亡情况;免疫组化检测caspase-3表达.结果 与S组比较,CPB组和PHA组T1～T3时血清S1003蛋白、TNF-α和IL-6的浓度升高,海马凋亡神经元增多,caspase-3表达上调（P＜0.05）,海马组织病理学损伤明显;与CPB组比较,PHA组T1～T3时血清S100β蛋白、TNF-α和IL-6的浓度降低,海马凋亡神经元减少,caspase-3表达下调（P＜0.05）,海马组织病理学损伤减轻.结论 α7nAChR激动剂可减轻CPB致大鼠脑损伤,其机制可能与抑制全身炎症反应和海马神经元凋亡有关.Objective To evaluate the effect of α7 nicotinic acetylcholine receptor （α7nAChR） agonists on brain injury induced by cardiopulmonary bypass （CPB） in rats.Methods Seventy-two pathogen-free adult male Sprague-Dawley rats,weighing 350-450 g,were randomly divided into 3 groups （n =24 each） using a random number table：sham operation group （group S）,CPB group,and α7nAChR agonist PHA568487 group （group PHA）.The rats underwent no CPB and were mechanically ventilated for 60 min in group S.CPB was performed for 60 min in CPB and PHA groups.At 30 min before CPB,PHA568487 0.8 mg/kg was injected intraperitoneally in group PHA,and the equal volume of normal saline was given in group CPB.Before CPB （T0）,immediately after termination of CPB （T1）,and at 2 and 6 h after operation （T2.3）,6 rats were sacrificed,and blood samples were collected from the internal jugular vein for determination of serum S100β protein,interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α） concentrations by enzyme-linked immunosorbent assay.Hippocampal tissues were obtained and stained with haematoxylin and eosin for microscopic examination of the pathologic changes and for detection of apoptosis in hippocampal neurons （by TUNEL） and caspase-3 expression （by immunohistochemistry）.Results Compared with group S,the concentrations of serum S100β protein,TNF-α and IL-6 were significantly increased,the number of apoptotic neurons was significantly increased,and the expression of caspase-3 was significantly up-regulated at T1-T3 （P〈0.05）,and the pathologic changes of hippocampal tissues were obvious in CPB and PHA groups.Compared with group CPB,the concentrations of serum S100β protein,TNF-α and IL-6 were significantly decreased,the number of apoptotic neurons was significantly reduced,and the expression of caspase-3 was significantly down-regulated at T1-T3 （P〈0.05）,and the pathologic changes of hippocampal tissues were significantly attenuated in group PHA.Conclusion α7nAChR agoni

关 键 词：胆碱能激动剂 心肺转流术 脑损伤 

分 类 号：R614[医药卫生—麻醉学]