右美托咪定预先给药对单肺通气大鼠肺组织caspase-12表达的影响

Effect of dexmedetomidine pretreatment on expression of caspase-12 in lung tissues undergoing one-lung ventilation in rats

目的 探讨右美托咪定预先给药对单肺通气大鼠肺组织caspase-12表达的影响.方法 清洁级SD雄性大鼠30只,6～8周龄,体重180～220 g,采用随机数字表法,将其分为3组（n=10）：双肺通气组（TLV组）、单肺通气组（OLV组）和右美托咪定组（Dex组）.TLV组行双肺通气2h.OLV组和Dex组均行右侧单肺通气1.5 h、双肺通气0.5 h.Dex组于单肺通气前60 min静脉输注右美托咪定3.0 μg·kg-1·h-1,60 min内输注完毕;OLV组和TLV组以等容量生理盐水替代.OLV组和Dex组于单肺通气45 min和双肺通气15 min时、TLV组于双肺通气15 min时记录气道峰压（Ppeak）和气道压（Paw）.随后处死大鼠并取左肺组织,测定肺组织湿重/干重（W/D）比值,HE染色法,观察肺组织病理学结果,透射电镜观察肺组织超微结构,TUNEL法检测肺组织细胞凋亡指数（AI）,RT-PCR法测定caspase-12 mRNA表达水平,Western blot法测定caspase-12表达水平.结果 与单肺通气45 min时比较,OLV组和Dex组双肺通气15 min时Ppeak和Paw降低（P＜0.05）.与TLV组比较,OLV组和Dex组肺组织W/D比值和AI升高,caspase-12及其mRNA表达上调（P＜0.01）.与OLV组比较,Dex组肺组织W/D比值和AI降低,caspase-12及其mRNA表达下调（P＜0.01）.Dex组肺组织病理学损伤较OLV组减轻.结论 右美托咪定预先给药减轻单肺通气大鼠急性肺损伤的机制与下调caspase-12表达,抑制细胞凋亡有关.

Objective To investigate the effect of dexmedetomidine pretreatment on the expression of caspase-12 in lung tissues undergoing one-lung ventilation （OLV） in rats.Methods Thirty male Sprague-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were randomly allocated into 3 groups （n=10 each） using a random number table： two-lung ventilation （TLV） group, OLV group and dexmedetomidine group （Dex group）.Bilateral lungs were ventilated for 2 h in group TLV.In OLV and Dex groups, unilateral lung was ventilated for 1.5 h followed by 0.5 h TLV.In group Dex, dexmedetomidine was infused intravenously at a rate of 3.0 μ g ·kg-1· h-1 over 60 min starting from 60 min prior to OLV.The equal volume of normal saline was given instead of dexmedetomidine in OLV and TLV groups.Peak airway pressure （Ppeak） and mean airway pressure （Paw） were recorded at 45 min of OLV and 15 min of TLV in OLV and Dex groups, and at 15 min of TLV in group TLV.The rats were then sacrificed, and left lungs were removed for microscopic examination of the pathologic changes （using HE staining） and the ultrastructure of lung tissues （with transmission electron microscope） and for determination of wet to dry lung weight ratio （W/D ratio）, cell apoptosis in lung tissues （by TUNEL）, caspase-12 mRNA expression （using real-time reverse transcriptase-polymerase chain reaction）, and caspase-12 expression （by Western blot）.Results Ppeak and Paw were significantly lower at 15 min of TLV than at 45 min of OLV in OLV and Dex groups （P〈0.05）.Compared to group TLV, W/D ratio and AI were significantly increased, and the expression of caspase-12 protein and mRNA was up-regulated in OLV and Dex groups （P〈0.01）.Compared to group OLV, W/D ratio and AI were significantly decreased, and the expression of caspase-12 protein and mRNA was down-regulated in group Dex （P 〈 0.01）.The pathologic changes of lung tissues were significantly alleviated in group Dex as compared with group OLV.Conclusion The mechanism by which dexmedetomidine pretreatment alleviates acute lung injury caused by OLV is associated with down-regulated expression of caspase-12 and inhibited cell apoptosis in rats.