TIPE2在脓毒症小鼠急性肺损伤内源性保护机制中的作用:与TREM-1/NLRP3炎症小体信号通路的关系  

Role of TIPE2 in endogenous protective mechanism of acute lung injury in septic mice:relationship with TREM-1/NLRP3 inflammasome signaling pathway

作　　者：王倩[1] 金振帅 孔倩[1] 袁敏[1] 明婷倩 吴晓静[1] Wang Qian;Jin Zhenshuai;Kong Qian;Yuan Min;Ming Tingqian;Wu Xiaojing(Department of Anesthesiology,Renmin Hospital,Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院麻醉科,430060

出　　处：《中华麻醉学杂志》2021年第12期1502-1505,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金(81901952)。

摘　　要：目的评价肿瘤坏死因子-α诱导蛋白家族8-样蛋白2(TIPE2)在脓毒症小鼠急性肺损伤内源性保护机制中的作用及其与髓样细胞表达触发受体-1(TREM-1)/NOD样受体蛋白3(NLRP3)炎症小体信号通路的关系。方法雄性野生型小鼠和TIPE2基因敲除小鼠各20只,分别采用随机数字表法分为野生型假手术组(WT-sham组)、野生型急性肺损伤组(WT-ALI组)、TIPE2基因敲除型假手术组(KO-sham组)及TIPE2基因敲除急性肺损伤组(KO-ALI组),每组10只。采用盲肠结扎穿孔法制备脓毒症小鼠急性肺损伤模型。术后24 h时腹主动脉采血样后处死小鼠取肺组织,光镜下观察肺组织病理学结果并行肺损伤评分,确定湿重/干重(W/D)比值,检测髓过氧化物酶(MPO)活性,采用Western blot法检测TIPE2、TREM-1、NLRP3、caspase-1和GSDMD的表达,采用ELISA法检测血清IL-1β和IL-18的浓度。结果与WT-sham组比较,WT-ALI组和KO-ALI组肺损伤评分、W/D比值、MPO活性、肺组织TREM-1、NLRP3、caspase-1、GSDMD表达水平及血清IL-1β和IL-18浓度升高,TIPE2表达下调(P<0.05);与WT-ALI组比较,KO-ALI组肺损伤评分、W/D比值、MPO活性、TREM-1、NLRP3、caspase-1、GSDMD表达水平及血清IL-1β和IL-18的浓度升高,TIPE2表达下调(P<0.05)。结论TIPE2参与了脓毒症小鼠急性肺损伤的内源性保护机制,与抑制TREM-1/NLRP3炎症小体信号通路激活有关。Objective To evaluate the role of tumor necrosis factor-alpha-induced protein-8 like-2(TIPE2)in endogenous protective mechanism of acute lung injury(ALI)in septic mice and the relationship with triggering receptor expressed on myeloid cells-1(TREM-1)/NOD-like receptor protein 3(NLRP3)inflammasome signaling pathway.Methods Twenty male wild-type mice and 20 TIPE2 knockout mice were divided into 4 groups using a random number table method:wild-type+sham operation group(group WT-sham),wild-type+ALI group(group WT-ALI),TIPE2-knockout+sham operation group(group KO-sham)and TIPE2-knockout+CLP group(group KO-ALI),with 10 mice in each group.The ALI model was established by cecal ligation and perforation(CLP)in septic mice.Mice were sacrificed after blood samples were obtained from the abdominal aorta at 24 h after CLP,and lung tissue specimens were obtained for microscopic examination of pathological changes(with a light microscope)which were scored and for determination of wet/dry weight ratio(W/D ratio),myeloperoxidase(MPO)activity,expression of TIPE2,TREM-1,NLRP3,caspase-1 and GSDMD(by Western blot),and concentrations of interleukin-1beta(IL-1β)and IL-18 in serum(by enzyme-linked immunosorbent assay).Results Compared with group WT-sham,the lung injury score,W/D ratio,MPO activity and concentrations of IL-1β and IL-18 in serum were significantly increased,the expression of TREM-1,NLRP3,caspase-1 and GSDMD was up-regulated,and the expression of TIPE2 was down-regulated in group WT-ALI and group KO-ALI(P<0.05).Compared with group WT-ALI,the lung injury score,W/D ratio,MPO activity and concentrations of IL-1β and IL-18 in serum were significantly increased,the expression of TREM-1,NLRP3,caspase-1 and GSDMD was up-regulated,and the expression of TIPE2 was down-regulated in group KO-ALI(P<0.05).Conclusion TIPE2 is involved in endogenous protective mechanism of ALI in septic mice,which is related to inhibition of activation of TREM-1/NLRP3 inflammasome signaling pathway.

关 键 词：肿瘤坏死因子-α诱导蛋白家族8-样蛋白2 脓毒症 急性肺损伤 NLR家族 热蛋白结构域包含蛋白3 髓样细胞表达触发受体-1 

分 类 号：R459.7[医药卫生—急诊医学] R563[医药卫生—治疗学]