右美托咪定对胸部撞击-失血性休克复苏致大鼠急性肺损伤时NLRP3炎症小体的影响  

Effects of dexmedetomidine on NLRP3 inflammasome during acute lung injury induced by blunt chest trauma and hemorrhagic shock-resuscitation in rats

作　　者：李灵丰[1] 吴晓静[1] 孔倩[1] 袁敏[1] 赵桂华 邱珍[1] 黄琴[1] 夏中元[1] Li Lingfeng;Wu Xiaojing;Kong Qian;Yuan Min;Zhao Guihua;Qiu Zhen;Huang Qin;Xia Zhongyuan(Department of Anesthesiology,Renmin Hospital,Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院麻醉科,430060

出　　处：《中华麻醉学杂志》2019年第6期754-757,共4页Chinese Journal of Anesthesiology

摘　　要：目的评价右美托咪定对胸部撞击-失血性休克复苏致大鼠急性肺损伤时NLRP3炎症小体的影响.方法 SPF级健康雄性SD大鼠45只,体重200~220 g,采用随机数字表法分为3组(n=15):假手术组(Sham组)、急性肺损伤组(ALI组)和右美托咪定组(Dex组).采用胸部撞击-失血性休克复苏的方法制备大鼠急性肺损伤模型.Dex组于胸部撞击后股静脉输注右美托咪定5μg·kg^-1·h^-1.于胸部撞击后6h时经股动脉留取血标本检测大鼠动脉血氧分压并计算氧合指数;ELISA法检测血清IL-1β和IL-18的浓度.股动脉放血处死大鼠并留取肺组织,观察肺组织病理学结果并进行肺损伤评分;采用Western blot法检测NLRP3、caspase-1和ASC的表达;采用比色法测定LDH和MPO活性.结果与Sham组比较,ALI组和Dex组PaO2和氧合指数降低,肺组织NLRP3、caspase-1和ASC表达上调,肺损伤评分、LDH和MPO活性、血清IL-1β和IL-18浓度升高(P<0.05);与ALI组比较,Dex组PaO2和氧合指数升高,肺组织NLRP3、caspase-1和ASC表达下调,肺损伤评分、LDH和MPO活性、血清IL-1β和IL-18浓度降低(P<0.05).结论右美托咪定减轻胸部撞击-失血性休克复苏致大鼠急性肺损伤的机制与抑制NLRP3炎症小体激活,降低炎性反应有关.Objective To evaluate the effects of dexmedetomidine on NLRP3 inflammasome during acute lung injury ( ALI ) induced by blunt chest trauma and hemorrhagic shock-resuscitation in rats. Methods Forty-five SPF healthy male Sprague-Dawley rats, weighing 200-220 g, were divided into 3 groups (n=15 each) using a random number table method: sham operation group (Sham group), ALI group and dexmedetomidine group ( Dex group). A rat model of ALI was established by blunt chest trauma and hemorrhagic shock-resuscitation. Dexmedetomidine 5 μg·kg^-1 ·h^-1 was infused into the femoral vein after blunt chest trauma in Dex group. Blood samples were collected from the femoral artery at 6 h after blunt chest trauma for measurement of arterial oxygen partial pressure and concentrations of pro-inflammatory cytokines interleukin-1beta ( IL-1β) and IL-18 in serum ( by enzyme-linked immunosorbent assay ). The oxygenation index was calculated. The rats were sacrificed and lungs were removed for examination of the pathological changes which were scored and for determination of the expression of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing CARD ( ASC) in lung tissues ( by Western blot) and ac-tivities of lactic dehydrogenase ( LDH) and myeloperoxidase ( MPO) in lung tissues ( by colorimetry). Re-sults Compared with Sham group, PaO2 and oxygenation index were significantly decreased, the expres-sion of NLRP3, caspase-1 and ASC was up-regulated, the activities of LDH and MPO were increased, and the concentrations of IL-1β and IL-18 in serum were increased in ALI group ( P<0. 05 ). Compared with ALI group, PaO2 and oxygenation index were significantly decreased, the expression of NLRP3, caspase-1 and ASC was down-regulated, the activities of LDH and MPO were decreased, and the concentrations of IL-1β and IL-18 in serum were decreased in ALI group ( P<0. 05). Conclusion Dexmedetomidine can al-leviate blunt chest trauma and hemorrhagic shock-resuscitation induced ALI in rats, and the mechanism is related to inhib

关 键 词：右美托咪啶 急性肺损伤 NLR家族 热蛋白结构域包含蛋白3 

分 类 号：R563[医药卫生—呼吸系统]