右美托咪定上调NLRC3改善大鼠机械通气相关性肺损伤  

Dexmedetomidine ameliorates ventilator-induced lung injury in rats via upregulating NLRC3

作　　者：乐林莉[1] 李娜[1] YUE Lin-li;LI Na(Department of Anesthesiology,Maternal and Child Health Hospital of Hubei Province,Wuhan HUBEI 430070,China)

机构地区：[1]湖北省妇幼保健院麻醉科,湖北武汉430070

出　　处：《中国新药与临床杂志》2024年第4期291-295,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：湖北省卫生健康委联合基金项目(WJ2019H278)。

摘　　要：目的观察右美托咪定对机械通气相关性肺损伤(VILI)大鼠NLR家族含CARD结构域蛋白3(NLRC3)表达的影响。方法36只SD大鼠随机分为正常对照组、模型组和右美托咪定组,每组各12只。接呼吸机机械通气制备VILI模型,右美托咪定组于制模前20 min静脉注射右美托咪定5μg·kg^(-1),随后以5μg·kg^(-1)·h^(-1)的剂量维持。正常对照组和模型组于制模前20 min静脉持续输注生理盐水0.5 mL·kg^(-1)·h^(-1)。光镜下观察各组大鼠肺组织病理学结果,检测肺组织湿重-干重比。Western blot和qRT-PCR法分别检测肺组织中NLRC3、NLR家族热蛋白结构域包含蛋白3(NLRP3)、凋亡相关斑点蛋白(ASC)、caspase-1、NF-κB p65的蛋白和mRNA表达,ELISA法测定血清中白细胞介素(IL)-1β、IL-18和IL-33的浓度。结果与正常对照组相比,模型组肺组织病理损伤严重,肺损伤定量评价指标(IQA)和肺组织湿重-干重比显著增加(P<0.05);肺组织中NLRC3蛋白和mRNA表达显著下调(P<0.05),NLRP3、ASC、caspase-1和NF-κB p65蛋白及mRNA的表达显著上调(P<0.05),血清中IL-1β、IL-18和IL-33的浓度显著增加(P<0.05)。与模型组比较,右美托咪定组肺组织病理损伤减轻,肺组织湿重-干重比和IQA降低(P<0.05),肺组织中NLRC3蛋白及mRNA表达显著增加(P<0.05),NLRP3、ASC、caspase-1和NF-κB p65蛋白和mRNA的表达显著下调(P<0.05),血清中IL-1β、IL-18和IL-33的浓度显著降低(P<0.05)。结论右美托咪定通过上调肺组织中NLRC3的表达改善大鼠VILI,其机制可能与抑制NLRP3炎症小体的激活有关。AIM To observe the effect of dexmedetomidine on the expression of NLR family CARD domain containing-3(NLRC3),a nucleotide oligomeric domain like receptor,in rats with ventilator-associated lung injury(VILI).METHODS A total of 36 SD rats were randomly divided into normal control group,model group,and dexmedetomidine group(n=12 in each group).VILI model were made by mechanical ventilation with a ventilator.The dexmedetomidine group was intravenously injected with dexmedetomidine 5μg·kg^(-1)at 20 minutes before VILI,then maintain a dose of 5μg·kg^(-1)·h^(-1).The normal control group and model group received continuous intravenous infusion of O.5mL·kg^(-1)·h^(-1)of physiological saline.The pathological results of lung tissue in each group of rats were observed under the light microscope and the wet dry weight ratio of lung tissue was detected.Western blot and qRT-PCR were used to detect of protein and mRNA expression of NLRC3,NLR family pyrin domain containing 3 protein(NLRP3).,apoptosis associated speck-like protein containing a CARD domain(ASC),caspase-1,and NF-kB p65.The protein level of IL-1β、IL-18 and IL-33 in serum were detected by ELISA.RESULTSS Compared with the normal control group,severe pathological damage in the lung tissue were showed in the model group,the wet to dry weight ratio and IQA of lung tissue increased significantly(P<0.05).NLRC3 protein and mRNA expression in lung tissue down regulated(P<0.05),NLRP3,ASC,caspase-1,and NF-kB p65 protein and mRNA upregulated significantly(P<0.05),and the concentration of IL-1β、IL-18 and IL-33 in serum increased significantly(P<0.05).Compared with the model group,the pathological damage of lung tissue in the dexmedetomidine group showed reduced,and the wet to dry weight ratio and IQA of lung tissue decreased(P<0.05),the expression of NLRC3 protein and mRNA in lung tissue increased significantly(P<0.05),NLRP3,ASC,caspase-1,and NF-kB p65 protein and mRNA downregulated(P<0.05),the concentrations of IL-1β,IL-18 and IL-33 reduced significantly(P<0.05).CO

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

分 类 号：R971.2[医药卫生—药品]