右美托咪定对老年患者单肺通气相关肺损伤时NLRP3/Caspase-1通路的影响

Effect of dexmedetomidine on NLRP3/Caspase-1 pathway in elderly patients with one-lung ventilation-related lung injury

目的探讨右美托咪定对老年患者行胸科手术单肺通气(OLV)所致肺损伤时NLRP3/Caspase-1通路的影响。方法拟行择期胸科手术患者64例,性别不限,年龄65~80岁,体重指数<30 kg/m^2,ASA分级Ⅱ级或Ⅲ级,采用随机数字表法分为对照组(C组)和右美托咪定组(D组),各32例。D组于麻醉诱导前15 min,静脉持续泵入右美托咪定负荷量0.5μg/kg,继以0.3μg/(kg·h)的速率持续泵入至术毕前30 min,C组给与等容量的生理盐水。分别于麻醉诱导前15 min(T 0)、OLV 30 min(T 1)、OLV 90 min(T 2)、恢复双肺通气即刻(T 3)行血气分析并计算氧合指数(OI),于T 1-3计算肺动态顺应性(Cdyn);于T 0-3利用ELISA检测外周血炎性因子IL-1β、IL-18和肺表面活性物质蛋白A(SP-A)浓度;于T 0-3利用qRT-PCR检测外周血单核细胞NLRP3 mRNA和Caspase-1 mRNA表达。结果与C组比较,D组T 1-3时OI和Cdyn升高(P<0.05);T 1-3时外周血IL-1β、IL-18和SP-A浓度降低(P<0.05);T 1-3时NLRP3 mRNA和Caspase-1 mRNA表达下调(P<0.05)。结论胸科手术老年患者围术期应用右美托咪定,可改善术中氧合及肺动态顺应性,降低炎性因子,减轻炎症反应,其机制可能与右美托咪定下调NLRP3/Caspase-1信号通路有关。

Objective To investigate the effect of dexmedetomidine on NLRP3/Caspase-1 pathway in elderly patients with lung injury caused by one-lung ventilation(OLV)during thoracic surgery.Methods 64 patients of both sexes,with elective thoracic surgery,aged 65~80 years old,with body mass index<30 kg/m 2,of ASA physical statusⅡorⅢ,scheduled for elective thoracic surgery under general anesthesia,were randomized into 2 groups(n=32 each)using a random number table:control group(group C)and dexmedetomidine group(group D).In group D,dexmedetomidine was infused intravenously at dose of 0.5μg/kg over 15 min before induction of anesthesia,followed by continuous infusion at a rate of 0.3μg/(kg·h)until 30 min before the end of operation,while the equal volume of normal saline was given in group C.Blood gas analyses were collected at 15 min before inducation of anesthesia(T 0),and at 30 min(T 1),90 min(T 2)of OLV,and immediately after two-lung ventilation(T 3),and oxygenated index(OI)was calculated.Lung dynamiccompliance(Cdyn)was calculated at T 1-3.The concentration of IL-1β,IL-18,SP-A in peripheral blood were detected by ELISA at T 0-3,and the expression of NLRP3 and Caspase-1 mRNA were detected by qRT-PCR at T 0-3.Results Compared with group C,OI and Cdyn in group D increased at T 1-3(P<0.05).The concentration of IL-1β,IL-18 and SP-A in peripheral blood decreased at T 1-3(P<0.05),the expression of NLRP3 and Caspase-1 mRNA was down-regulated at T 1-3(P<0.05).Conclusion The perioperative application of dexmedetomidine in elderly patients undergoing thoracic surgery can improve intraoperative oxygenation and pulmonary dynamic compliance,reduce inflammatory factors and alleviate inflammation.The mechanism may be related to the down-regulation of NLRP3/Caspase-1 signaling pathway by dexmedetomidine.