PI3K∕Akt信号通路在右美托咪定减轻体外循环大鼠肺缺血再灌注损伤的作用  

Role of PI3K/Akt signaling pathway in induced reduction of lung ischemia-reperfusion injury in rats undergoing cardiopulmonary bypass

作　　者：李倩[1] 窦雪娇[1] 韩明[1] 李健 谢菲 何苗[4] 张红[1] Li Qian;Dou Xuejiao;Han Ming;Li Jian;Xie Fei;He Miao;Zhang Hong(Department of Anesthesiology,Affiliated Hospital of Zunyi Medical College,Zunyi 563000,China;Department of Anesthesiology,Huai'an First Hospital Affiliated to Nanjing Medical University,Huai'an 223300,China;Department of Intensive Care Unit,First People's Hospital of Zunyi,Zunyi 563000,China;Department of Anesthesiology,Affiliated Hospital of Chengdu University,Chengdu 610081,China)

机构地区：[1]遵义医学院附属医院麻醉科,563000 [2]南京医科大学附属淮安第一医院麻醉科,223300 [3]遵义市第一人民医院重症医学科,563000 [4]成都大学附属医院麻醉科,610081

出　　处：《中华麻醉学杂志》2018年第7期803-807,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81460074);贵州省麻醉学研究生工作站(黔教研合GZZ字【2016】05)。

摘　　要：目的 评价磷脂酰肌醇3激酶∕蛋白激酶B( PI3K∕Akt)信号通路在右美托咪定减轻体外循环(CPB)致大鼠肺缺血再灌注损伤中的作用.方法 健康成年雄性SD大鼠24只,体重350~450 g,采用随机数字表法分为3组(n=8):缺血再灌注组(I∕R组)、右美托咪定组(D组)和右美托咪定+渥曼青霉素组(D+W组).建立CPB并循环10 min时开胸,阻断左肺门45 min后恢复灌注. D组于阻断左肺门前10 min时尾静脉注射右美托咪定3 μg∕kg,之后以1. 5 μg·kg-1·h-1的速率静脉输注至CPB结束;D+W组于阻断左肺门前10 min时尾静脉注射右美托咪定3 μg∕kg,之后以1. 5 μg·kg-1·h-1的速率静脉输注至 CPB 结束,同时股静脉注射渥曼青霉素 15 μg∕kg,之后以 2. 0 μg·kg-1·min-1的速率静脉输注至CPB结束.分别于CPB前即刻( T1)、开放左肺门即刻( T2)和CPB结束后1. 5 h时(T3)采集动脉血样行血气分析,计算氧合指数( OI)和呼吸指数( RI).于T3时处死大鼠留取左肺组织,光镜下观察病理学结果,并行肺损伤评分,采用流式细胞仪测定细胞凋亡率,采用Western blot法测肺组织 Akt、Bad、活化的 caspase-3和磷酸化 Akt(p-Akt)、磷酸化 Bad(p-Bad)的表达水平.结果 与T1时比较,3组T2和T3时点OI降低,RI升高( P<0. 05);与T2时比较,3组T3时OI降低,RI升高(P<0. 05);与I∕R组比较,D组T3时OI升高,RI降低,肺损伤评分及细胞凋亡率降低,肺组织p-Akt∕Akt比值和p-Bad∕Bad比值升高,活化的caspase-3表达下调,D+W组T2时点OI降低,RI升高(P<0. 05);与D组比较,D+W组T2和T3时点OI降低,RI升高,肺损伤评分及细胞凋亡率升高,肺组织p-Akt∕Akt比值和p-Bad∕Bad比值降低,活化的caspase-3表达上调(P<0. 05).结论 右美托咪定可通过激活PI3K∕Akt信号通路,抑制细胞凋亡,减轻CPB大鼠肺缺血再灌注损伤.Objective To evaluate the role of PI3K/Akt signaling pathway in dexmedetomidine-induced reduction of lung ischemia-reperfusion (I/R)injury in rats undergoing cardiopulmonary bypass (CPB).Methods Twenty-four healthy adult male Spragne-Dawley rats,weighing 350-450g,were divided into 3groups (n =8 each)using a random number table method:group I/R,dexmedetomidine group (group D)and dexmedetomidine plus wortmannin group (group D+W).Rats were anesthetized with pento-barbital sodium.Lung I/R was induced by clamping the left hilum of lung for 60min starting from 10min of CPB,followed by 120-min reperfusion.Dexmedetomidine was injected via the tail vein in a dose of 3μg/kg at 10min before clamping the left hilum of lung,followed by a continuous infusion of 1.5μg·kg^-1·h^-1 until the end of CPB in group D.Dexmedetomidine was injected via the tail vein in a dose of 3μg/kg at 10 min before clamping the left hilum of lung,followed by a continuous infusion of 1.5μg·kg^-1·h^-1 until the end of CPB,and wortmannin was simultaneously injected via the tail vein in a dose of 15μg/kg,followed by a continuous infusion of 2.0μg·kg^-1·min^-1 until the end of CPB in group D+W.Arterial blood samples were collected immediately before CPB (T1),immediately after opening the left hilum of lung (T2)and at i.5h after the end of CPB (T3),and oxygenation index (OI)and respiratory index (RI) were calculated.The rats were Sacrificed at T3,and the left lung was removed for examination of the patho- logical changes which were scored and for determination of apoptosis rate (by flow cytometry)and Akt, Bad,activated caspase-3,phosphorylated Akt (p-Akt)and phosphorylated Bad (p-Bad)in lung tissues (by Western blot).Results Compared with the baseline at T1,OI was significantly decreased and RI was increased at T2 and T3 in the three groups (P<0.05).OI was significantly decreased and RI was increased at T3than at T2in the three groups (P<0.05).Compared with group I/R,OI was significantly increased and RI was decreased at T3,the pathological dam

关 键 词：右美托咪啶 1-磷脂酰肌醇3-激酶 蛋白质丝氨酸苏氨酸激酶 心肺转流术 再灌注损伤 肺 

分 类 号：R614[医药卫生—麻醉学]