右美托咪定对小鼠呼吸机相关性肺损伤时NLRP3炎症小体活性的影响  

Effect of dexmedetomidine on NLRP3 inflammasome activity in mice with ventilator-induced lung injury

作　　者：陈小萍[1] 葛亚丽[1] 黄天丰 高巨[1] Chen Xiaoping;Ge Yali;Huang Tianfeng;Gao Ju(Department of Anesthesiology,Subei People′s Hospital of Jiangsu Province Institute of Anesthesia,Emergency and Critical Care,Subei People′s Hospital of Jiangsu Province,Yangzhou 225000,China)

机构地区：[1]江苏省苏北人民医院麻醉科,江苏省苏北人民医院麻醉与急危重症研究所,扬州225000

出　　处：《中华麻醉学杂志》2020年第1期56-60,共5页Chinese Journal of Anesthesiology

摘　　要：目的评价右美托咪定对小鼠呼吸机相关性肺损伤(VILI)时NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体活性的影响。方法SPF级雄性C57BL/6J小鼠84只,体重25~30 g,2~3月龄,采用随机数字表法分为3组(n=28):对照组(C组)、VILI组和右美托咪定组(D组)。C组保留自主呼吸,VILI组和D组机械通气4 h;D组于气管插管前静脉输注右美托咪定负荷剂量1.0μg/kg 20 min,并以1.0μg·kg^-1·h^-1的速率维持4 h。于气管插管前、机械通气1、2及4 h(T1-4)时经股动脉采集血样测定PaO2。T4时每组取8只小鼠,处死后取肺,制备支气管肺泡灌洗液(BALF),检测总蛋白、IL-1β和IL-18浓度;取肺组织,计算湿重/干重比值(W/D比值),行肺损伤评分,采用RT-PCR法检测IL-1β和IL-18的mRNA表达水平,采用Western blot法检测NLRP3、凋亡相关微粒蛋白(ASC)和caspase-1的表达水平。各组剩余20只小鼠用于观察24 h生存情况。结果与C组比较,VILI组和D组T3、T4时PaO2降低,24 h生存率降低,肺损伤评分、W/D比值、BALF总蛋白、IL-1β和IL-18浓度升高,肺组织NLRP3、ASC、caspase-1、IL-1βmRNA和IL-18 mRNA表达上调(P<0.05);与VILI组比较,D组24 h生存率升高,肺损伤评分、W/D比值、BALF总蛋白浓度、IL-1β、IL-18浓度降低,肺组织NLRP3、ASC、caspase-1、IL-1βmRNA和IL-18 mRNA表达下调(P<0.05)。结论右美托咪定减轻小鼠VILI时炎症反应的机制可能与其抑制NLRP3炎症小体活性有关。Objective To evaluate the effect of dexmedetomidine on the activity of nucleotide-binding oligomerization domain-like receptor containing pyrin domain(NLRP3)inflammasome in ventilator-induced lung injury(VILI)in mice.Methods Eighty-four male SPF C57BL/6J mice,weighing 25-30 g,aged 2-3 months,were divided into 3 groups(n=28 each)using a random number table method:control group(C group),VILI group and dexmedetomidine group(D group).The mice were tracheostomized and spontaneous breathing was maintained in group C,while the other mice were tracheostomized and mechanically ventilated for 4 h in VILI and D groups.Dexmedetomidine was infused in a loading dose of 1.0μg/kg for 20 min before intubation followed by continuous infusion of 1.0μg·kg^-1·h^-1 for 4 h in group D.Blood samples were taken from the femoral artery for blood gas analysis before intubation and at 1,2 and 4 h of mechanical ventilation(T1-4),and PaO2 was recorded for detection of PaO2.Eight mice were selected at T4 and sacrificed,and the broncho-alveolar lavage fluid(BALF)was collected for determination of the concentration of total protein,interleukin-1β(IL-1β)and interleukin-18(IL-18).The lung tissues were removed for microscopic examination of pathologic changes which were scored and for determination of the wet to dry weight(W/D)ratio,expression of IL-1βand IL-18 mRNA(by real-time polymerase chain reaction),and expression of NLRP3,apoptosis-associated speck-like protein containing CARD(ASC),and caspase-1(by Western blot).The other 20 mice in each group were observed for the 24-h survival rate.Results Compared with group C,PaO2 at T3 and T4 and 24-h survival rate were significantly decreased,and the lung injury score,W/D ratio,and concentrations of total protein,IL-1β,and IL-18 in BALF were increased,and the expression of NLRP3,ASC,caspase-1,IL-1βmRNA and IL-18 mRNA was up-regulated in VILI and D groups(P<0.05).Compared with group VILI,the 24-h survival rate was significantly increased,the lung injury score,W/D ratio,and concentrations of tot

关 键 词：NLR家族 热蛋白结构域包含蛋白3 右美托咪啶 呼吸机相关性肺损伤 

分 类 号：R614[医药卫生—麻醉学]