敲除巨噬细胞移动抑制因子在脓毒症小鼠肺损伤中的作用及其与NLRP3炎症小体的关系  

Roles of macrophage migration inhibitory factor in lung injury of sepsis mice and its relationship with NLRP3 inflammatome

作　　者：林雪容 王佳[1] 郭占敏 张志斌[1] Xuerong;WANG Jia;GUO Zhanmin;ZHANG Zhibin(Department of Emergency,the First Affiliated Hospital of Hebei North College,Zhangjiakou 075000,China)

机构地区：[1]河北北方学院附属第一医院急诊科,张家口075000

出　　处：《浙江医学》2024年第23期2480-2485,I0005,共7页Zhejiang Medical Journal

基　　金：河北省医学科学研究课题计划项目(20240348)。

摘　　要：目的探讨敲除巨噬细胞移动抑制因子(MIF)在脓毒症小鼠肺损伤中的作用及其与核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3(NLRP3)炎症小体的关系。方法将20只野生型(WT)小鼠和20只MIF敲除(KO)小鼠均采用随机数字表法分为WT对照组和WT肺损伤组、KO对照组和KO肺损伤组,每组各10只。WT肺损伤组和KO肺损伤组采用盲肠结扎穿孔术制备脓毒症肺损伤模型,WT对照组和KO对照组进行假手术操作,造模24 h后处死小鼠并检测肺组织湿重(W)/干重(D)比值,采用HE染色观察肺组织病理形态并进行肺损伤评分,酶联免疫吸附法检测血清IL-1β、IL-18、Gasder-min氨基末端(GSDMD-N)水平,Western blot法检测肺组织中MIF、NLRP3、裂解型半胱氨酸的天冬氨酸蛋白水解酶-1(cas-pase-1)、IL-1β、IL-18、GSDMD-N蛋白表达水平。结果WT肺损伤组的肺组织W/D比值,肺损伤评分,血清IL-1β、IL-18、GSDMD-N水平,肺组织MIF、NLRP3、裂解型caspase-1、IL-1β、IL-18、GSDMD-N蛋白表达水平均高于WT对照组和KO肺损伤组(均P<0.05)。结论MIF KO能减轻脓毒症小鼠肺损伤,其作用机制可能与抑制NLRP3炎症小体有关。Objective To investigate the roles of macrophage migration inhibitory factor(MIF)in lung injury of sepsis mice and its relationship with nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3)inflammatome.Methods Twenty wild-type(WT)mice and twenty MIF knockout(KO)mice were randomly divided into WT control group,WT lung injury group,KO control group and KO lung injury group with 10 mice in each group.The lung injury model of sepsis was prepared by cecal ligation and perforation in WT and KO groups.Animals were sacrificed 24 hours after modelling,the dry weight to wet weight(W/D)ratio of lung tissue was calculated;the pathological changes of lung tissue was observed with HE staining and lung injury score was analyzed.The serum levels of IL-1β,IL-18,Gasdermin-N terminal(GSDMD-N)were detected with ELISA;the protein expression levels of MIF,NLRP3,cysteinyl aspartate specific proteinase-1(caspase-1),IL-1β,IL-18 and GSDMD-N in lung tissues were detected with Western blot.Results The W/D level,lung injury score,serum IL-1β,IL-18 and GSDMD-N contents,the protein expression levels of MIF,NLRP3,cleaved caspase-1,IL-1β,IL-18 and GSDMD-N in lung tissues of WT lung injury group were significantly higher than those of WT control group and KO injury group(all P<0.05).Conclusion MIF KO reduces lung injury of sepsis mice,which may be related to the inhibition of NLRP3 inflammasome.

关 键 词：巨噬细胞移动抑制因子 脓毒症 肺损伤 核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3 炎症小体 

分 类 号：R459.7[医药卫生—急诊医学] R-332[医药卫生—治疗学]