激活CB2R抑制凋亡减轻肺缺血再灌注损伤的机制研究  

Mechanism of inhibiting apoptosis by activating CB2R to alleviate lung ischemia-reperfusion injury

作　　者：马琪 黄伟 李雪寒 王儒蓉[1] MA Qi;HUANG Wei;LI Xue-han;WANG Ru-rong(Department of Anesthesiology,West China Hospital,Sichuan University,Chengdu Sichuan 610041;Department of Anesthesiology,West China Second Hospital,Sichuan University,Chengdu Sichuan 610044,China)

机构地区：[1]四川大学华西医院麻醉科,四川成都610041 [2]四川大学华西第二医院麻醉科,四川成都610044

出　　处：《蚌埠医学院学报》2023年第8期1030-1035,共6页Journal of Bengbu Medical College

基　　金：国家自然科学基金项目(81900064)。

摘　　要：目的:建立C57BL/6小鼠肺缺血再灌注模型,选用大麻素2(CB2)受体激动剂JWH-133和拮抗剂AM-630预处理,研究CB2R在缺血再灌注所致肺损伤中的作用。方法:48只小鼠随机分为4组:假手术组(Sham组)、缺血再灌注组(I/R组)、JWH133组和AM630+JWH133组,每组各12只。I/R组小鼠开胸后采用血管钳夹闭左侧肺门1 h,松开血管钳后再灌注2 h,Sham组小鼠开胸后只分离但不夹闭左侧肺门,双肺通气3 h;JWH133组阻断肺门前5 min于腹腔内注射JWH-133(5 mg/kg),使用血管钳夹闭左侧肺门缺血1 h,松开后再灌注2 h;AM630+JWH133组在注射JWH-133前30 min腹腔内注射AM-630(2 mg/kg),其余同JWH133组。每组小鼠再随机分为2个亚组,分别用于血气分析和肺湿干比测定、肺组织病理学检查和凋亡相关蛋白(Bcl-2、Bax和caspase-9)的检测。结果:与I/R组比较,JWH133组小鼠氧合指数增加,肺湿干比和肺损伤病理学评分降低,HE染色显示肺组织结构明显改善,Bcl-2蛋白表达明显增加,Bax和caspase-9蛋白表达明显降低。在给予JWH-133前腹腔内注射AM-630预处理后,JWH-133的上述作用被逆转。结论:腹腔内注射CB2R激动剂JWH-133可以抑制小鼠肺组织细胞凋亡,明显减轻肺缺血再灌注损伤。细胞凋亡可能参与了激活CB2R所介导的肺保护作用。Objective:To establish a lung ischemia-reperfusion(I/R)model in C57BL/6 mice,and to study the role of cannabinoid 2(CB2)receptor in lung I/R injury by pretreatment with CB2 receptor agonist JWH-133 and antagonist AM-630.Methods:Forty-eight mice were randomly divided into the following 4 groups:Sham group,I/R group,JWH133 group and AM630+JWH133 group,with 12 mice in each group.In Sham group,the hilum was separated by thoracotomy without clamping,and then ventilated for 3 hours.In the I/R group,after thoracotomy,the left pulmonary hilum was clamped with vascular forceps for 1 hour,and reperfusion was performed for 2 hours after release.JWH133 group:JWH-133(5 mg/kg)was intraperitoneal injected 5 minutes after clamping of the pulmonary hilum,and the left hilum was occlusioned for 1 hour of ischemia,and then reperfusion was performed for 2 hours after release;AM630+JWH133 group.AM-630(2 mg/kg)was intraperitoneally injected 30 minutes before JWH-133 injection,and the rest was the same as JWH133 group.Each group was then randomly divided into two subgroups for blood gas analysis,lung wet-dry ratio determination,lung histopathological examination and apoptosis-related proteins(Bcl-2,Bax,caspase-9)detection.Results:Compared with I/R group,oxygenation index was increased,lung wet-dry ratio and pathological score of lung injury were significantly decreased in JWH133 group,lung tissue structure was improved by HE staining,the expression of Bcl-2 was significantly increased,and the expression of caspase-9 and Bax was significantly decreased.These effects were reversed by intraperitoneal injection of AM-630 prior to JWH-133 administration.Conclusions:Intraperitoneal injection of CB2 receptor agonist JWH-133 can inhibit the apoptosis of lung tissue in mice,and obviously alleviate the lung ischemia-reperfusion injury.Apoptosis may be involved in activating CB2 receptor-mediated lung protection.

关 键 词：肺缺血再灌注损伤 凋亡 大麻素2受体 

分 类 号：R655[医药卫生—外科学]