摘要
目的采用离体实验评价右美托咪定对大鼠肺缺血再灌注时细胞焦亡的影响。方法成年雄性SD大鼠,体重250~320 g,采用IL-2离体肺灌流系统制备大鼠离体肺灌注模型。取离体灌注模型制备成功的肺脏30个,采用随机数字表法分为3组(n=10):对照组(C组)、缺血再灌注组(I/R组)和右美托咪定组(DEX组)。C组K-H液持续灌注150 min;I/R组和DEX组灌注15 min后,停止通气和灌流60 min,继续通气和复灌75 min制备肺缺血再灌注损伤模型;DEX组在复灌开始时于K-H液中加入右美托咪定10 nmol/L。取肺组织,测定湿重/干重比值(W/D比值),光镜下观察病理学结果,并计算肺泡损伤率(IAR),电镜下观察超微结构。分别采用Western blot法与RT-PCR法检测肺组织细胞焦亡相关因子NOD样受体家族蛋白3(NLRP3)、caspase-1、IL-1β、IL-18及消皮素D(GSDMD)及其mRNA的表达水平。结果与C组比较,I/R组和DEX组肺组织W/D比值和IAR升高,NLRP3、caspase-1、IL-1β、IL-18及GSDMD及其mRNA表达上调(P<0.05)。与I/R组比较,DEX组肺组织W/D比值和IAR降低,NLRP3、caspase-1、IL-1β、IL-18及GSDMD及其mRNA表达下调(P<0.05),病理学损伤减轻。结论右美托咪定减轻大鼠离体肺缺血再灌注损伤的机制可能与抑制细胞焦亡有关。
Objective To evaluate the effect of dexmedetomidine on pyroptosis during lung ischemia-reperfusion(I/R)in rats.Methods Adult male Sprague-Dawley rats,weighing 250-320 g,were used in this study.The model of isolated lung perfusion was established using an IL-2 Isolated Perfused Rat or Guinea Pig Lung System after the rats were anesthetized.Thirty lungs in which an ex vivo lung perfusion model was successfully established were divided into 3 groups(n=10 each)by a random number table method:control group(C group),I/R group and dexmedetomidine group(DEX group).The lungs were continuously perfused with K-H solution for 150 min in C group.After 15 min of perfusion,lungs were subjected to 60-min suspension of ventilation and perfusion,followed by 75 min of reperfusion and ventilation to establish the model of lung I/R injury in I/R and DEX groups.In DEX group,dexmedetomidine 10 nmol/L was added to K-H solution at the beginning of reperfusion.Lung tissues were obtained for determination of wet/dry weight ratio(W/D ratio)and for examination of pathological changes(with a light microscope)and ultrastructure(using an electron microscope),and the alveolar damage rate(IAR)was calculated.The expression of pyroptosis-related factors including NOD-like receptor family protein 3(NLRP3),caspase-1,interleukin-1β(IL-1β),IL-18 and gasdermin D(GSDMD)protein and mRNA was detected by Western blot or by real-time polymerase chain reaction.Results Compared with C group,the W/D ratio and IAR in lung tissues were significantly increased,and the expression of NLRP3,caspase-1,IL-1β,IL-18 and GSDMD protein and mRNA was up-regulated in I/R and DEX groups(P<0.05).Compared with I/R group,the W/D ratio and IAR in lung tissues were significantly decreased,the expression of NLRP3,caspase-1,IL-1β,IL-18 and GSDMD protein and mRNA was down-regulated(P<0.05),and the pathological changes were significantly attenuated in DEX group.Conclusion The mechanism by which dexmedetomidine reduces isolated rat lung I/R injury may be related to inhibiting pyropt
作者
姚翔燕
张加强
李璐
杜献慧
齐艳艳
马丽斌
杨亚利
张江玲
李宁
张会
Yao Xiangyan;Zhang Jiaqiang;Li Lu;Du Xianhui;Qi Yanyan;Ma Libin;Yang Yali;Zhang Jiangling;Li Ning;Zhang Hui(Department of Anesthesia and Perioperative Medicine,Henan Provincial People′s Hospital,Zhengzhou 450003,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2019年第8期915-919,共5页
Chinese Journal of Anesthesiology
