α7nAChR激动剂对体外循环大鼠肠保护的机制:与肠神经胶质细胞活性的关系  

Mechanism ofα7nAChR agonist-induced protection in intestine in rats undergoing cardiopulmonary bypass:relationship with activity of enteric glial cells

作　　者：范嘉宁 伊小婷 孙莹杰 常畅 张霄燕 Fan Jianing;Yi Xiaoting;Sun Yingjie;Chang Chang;Zhang Xiaoyan(Postgraduate Training Base of Jinzhou Medical University in The General Hospital of Northern Theater Command,Shenyang 110016,China;Department of Anesthesiology,General Hospital of Northen Theater Command,Shenyang 110016,China)

机构地区：[1]锦州医科大学北部战区总医院研究生培养基地,沈阳110016 [2]北部战区总医院麻醉科,110016

出　　处：《中华麻醉学杂志》2020年第7期809-812,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金面上项目(81471121);辽宁省自然科学基金(201602790)。

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)大鼠肠保护的机制与肠神经胶质细胞(EGCs)活性的关系。方法清洁级健康成年雄性SD大鼠72只,体重400~500 g,按照随机数字表法分为3组(n=24):假手术组(S组)、CPB组(C组)和α7nAChR激动剂PHA568487+CPB组(P组)。P组腹腔注射PHA5684870.8 mg/kg,30 min后建立CPB模型。于CPB开始即刻(T0)、CPB 1 h(T1)和停CPB后2 h(T2)、停CPB后6 h(T3)时处死大鼠,取肠组织,观察病理学结果,Western blot法检测ZO-1、occludin及胶质纤维酸性蛋白(GFAP)、钙结合蛋白(S-100β蛋白)的表达;免疫组化法观察T2时GFAP阳性表达情况。结果与S组比较,C组和P组T1-3时GFAP和S-100β蛋白表达上调,ZO-1和occludin表达下调(P<0.05),GFAP表达阳性增加,肠组织损伤加重;与C组比较,P组T1-3时GFAP、ZO-1、occludin表达上调,S-100β蛋白表达下调(P<0.05),GFAP表达阳性增强,肠组织损伤减轻。结论α7nAChR激动剂减轻CPB大鼠肠损伤的机制可能与激活EGCs,改善肠屏障功能有关。Objective To evaluate the mechanism ofα7 nicotinic acetylcholine receptor(α7nAChR)agonist-induced protection of the intestine in rats undergoing cardiopulmonary bypass(CPB)and the relationship with the activity of enteric glial cells(EGCs).Methods Seventy-two clean-grade adult male Sprague-Dawley rats,aged 400-500 g,were divided into 3 groups(n=24 each)using a random number table method:sham operation group(group S),CPB group(group C)andα7nAChR agonist PHA568487 plus CPB group(group P).In group P,PHA5684870.8 mg/kg was intraperitoneally injected,and 30 min later CPB model was established.At the beginning of CPB(T0),at 1 h of CPB(T1),and at 2 and 6 h after termination of CPB(T2,3),the rats were sacrificed,and intestinal tissues were obtained for examination of the pathological changes and for determination of the expression of ZO-1,occludin,glial fibrillary acidic protein(GFAP),and calcium-binding protein(S-100βprotein)by Western blot.The immunohistochemical method was used to observe the positive expression of GFAP at T2.Results Compared with group S,the expression of GFAP and S-100βprotein was significantly up-regulated,and the expression of ZO-1 and occludin was down-regulated at T1-3(P<0.05),the positive expression of GFAP was increased,and the intestinal tissue injury was accentuated in C and P groups.Compared with group C,the expression of GFAP,ZO-1 and occludin was significantly up-regulated,and the expression of S-100βprotein was down-regulated at T1-3(P<0.05),the positive expression of GFAP was increased,and the intestinal tissue injury was reduced in group P.Conclusion The mechanism by whichα7nAChR agonist attenuates intestinal injury may be related to activating EGCs and improving intestinal barrier function in rats undergoing CPB.

关 键 词：胆碱能激动剂 心肺转流术 肠 神经胶质 

分 类 号：R574[医药卫生—消化系统]