右美托咪定通过调控SIGIRR/NF-κB信号对脂多糖诱导的大鼠急性肺损伤的影响  

Effects of dexmedetomidine on acute lung injury induced by lipopolysaccharide by regulating SIGIRR/NF-κB signaling

作　　者：王鹏程 王震[1] 代彦文 王涛 WANG Peng-cheng;WANG Zhen;DAI Yan-wen;WANG Tao(Dept of Anesthesiology,Zhumadian Central Hospital of Huanghuai University,Zhumadian Henan 463003,China;Dept of Pharmacology,School of Pharmacy,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]黄淮学院直属附属驻马店市中心医院麻醉科,河南驻马店463003 [2]郑州大学药学院药理学系,河南郑州450001

出　　处：《中国药理学通报》2021年第8期1076-1080,共5页Chinese Pharmacological Bulletin

基　　金：河南省医学科技攻关计划项目(No 201602135)。

摘　　要：目的探究右美托咪定(dexmedetomidine,DEX)对脂多糖(LPS)诱导的大鼠急性肺损伤(ALI)的影响及其作用机制。方法实验分为正常对照组(Control)、DEX对照组(DEX)、LPS诱导大鼠急性肺损伤组(LPS)以及LPS+DEX处理组(LPS+DEX)。待造模成功后24 h检测各组大鼠肺组织湿/干质量比(W/D)、支气管肺泡灌洗液(BALF)IL-1β、TNF-α和IL-6含量;HE染色观察肺组织病理学改变;免疫组化和Western blot检测SIGIRR和NF-κB表达。结果与Control组相比,LPS组肺组织W/D以及BALF中IL-1β、IL-6和TNF-α含量均增加(P<0.01),肺组织出现明显的ALI病理损伤,且SIGIRR表达降低(P<0.01),NF-κB磷酸化活化增强(P<0.01);与LPS组相比,LPS+DEX组肺组织W/D以及BALF中IL-1β、IL-6和TNF-α含量均降低(P<0.05或P<0.01);肺组织病理性损伤明显减轻,且SIGIRR表达增加,NF-κB磷酸化活化降低(P<0.01)。结论右美托咪定可能通过降低SIGIRR降解,抑制NF-κB活化,降低炎症反应,从而减轻脂多糖诱导的大鼠急性肺损伤。Aim To explore the effect of dexmedetomidine(DEX)on acute lung injury(ALI)induced by lipopolysaccharide(LPS)in rats and its mechanism.Methods The experiment included normal control group(Control),DEX control group(DEX),LPS-induced acute lung injury group(LPS)and LPS+DEX treatment group(LPS+DEX).Twenty-four hours after the successful modelling,the wet/dry weight ratio(W/D)of the lung tissues of each group and the content of inflammatory cytokines IL-1β,TNF-αand IL-6 in the bronchoalveolar lavage fluid(BALF)were measured;Hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissues;immunohistochemistry and Western blot were used to detect the expression of SIGIRR and NF-κB in lung tissues.Results Compared with control group,the levels of IL^(-1)β,IL-6 and TNF-αin lung tissues of LPS group and BALF increased(P<0.01).The lung tissues showed obvious pathological damage of ALI,and the expression of SIGIRR was reduced(P<0.01),the expression of phosphorylation activation of NF-κB increased(P<0.01).Compared with LPS group,the W/D of lung tissues in LPS+DEX group and IL-1β,IL-in BALF 6 and TNF-αcontent were reduced(P<0.05 or P<0.01).The pathological damage of lung tissues was significantly reduced,SIGIRR expression increased,and the activation of NF-κB phosphorylation decreased(P<0.01).Conclusions Dexmedetomidine can reduce SIGIRR degradation,inhibit the activation of NF-κB and reduce the inflammation,thereby reducing the acute lung injury induced by lipopolysaccharide in rats.

关 键 词：急性肺损伤 脂多糖 右美托咪定 单免疫球蛋白白细胞介素1受体相关蛋白 NF-κB 炎症反应 

分 类 号：R-332[医药卫生] R322.35