IL-37腹腔注射对脓毒血症小鼠心肌损伤的影响及机制  

Intraperitoneal injection of IL-37 ameliorates myocardial injury in mice with sepsis

作　　者：徐嵘 王蕾艳 米柯霖 曹新冉 赵刚 苑海涛 XU Rong;WANG Leiyan;MI Kelin;CAO Xinran;ZHAO Gang;YUAN Haitao(Cheeloo College of Medicine,Shandong University,Jinan 250021,China;不详)

机构地区：[1]山东大学齐鲁医学院,济南250021 [2]山东第一医科大学附属省立医院心内科

出　　处：《山东医药》2022年第22期33-36,共4页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81770382);山东省自然科学基金资助项目(ZR2020MH031);山东省重点研发项目(2018GSF118109);济南市临床医学科技创新计划项目(201907033)。

摘　　要：目的探讨腹腔注射IL-37对脓毒症小鼠心肌损伤的影响。方法将30只雄性C57BL/6J小鼠随机分为对照组、LPS组、IL-37组,每组10只。LPS组小鼠腹腔注射脂多糖(LPS)20 mg/kg,构建脓毒症模型;IL-37组小鼠腹腔注射LPS 20 mg/kg及IL-371 mg/kg;对照组小鼠行腹腔注射等体积无菌生理盐水。通过心脏超声评估各组小鼠心功能,通过HE染色评估各组小鼠心肌组织病理损伤程度;应用免疫组化法检测心肌组织中炎性因子IL-1β、IL-6、TNF-α表达;通过免疫组化及蛋白免疫印迹法分析NLRP3炎症小体及相关信号通路的蛋白表达。结果与对照组相比,LPS组小鼠左心室射血分数(LVEF)、缩短分数(FS)均降低(P均<0.05),与LPS组相比,IL-37组小鼠LVEF、FS均升高(P均<0.05)。与对照组相比,LPS组中小鼠心肌组织结构排列紊乱,肌膜破裂,伴有间质充血和水肿;与LPS组相比,IL-37组小鼠心功能及心肌组织病理损伤明显得到改善。LPS组、对照组、IL-37组小鼠心肌组织中炎性因子IL-1β表达分别为20.12±1.89、1.00±0.56、8.09±2.89,IL-6表达分别为36.56±5.17、1.00±0.25、9.92±1.37,TNF-α表达分别为20.87±6.35、1.00±0.44、6.23±1.29,小鼠心肌组织中炎性因子IL-1β、IL-6、TNF-α表达LPS组高于对照组(P均<0.05),IL-37组低于LPS组(P均<0.05)。LPS组、对照组、IL-37组小鼠心肌组织中NLRP3蛋白表达分别为6.42±0.16、1.00±0.21、5.39±0.11,小鼠心肌组织中NLRP3蛋白表达LPS组高于对照组(P<0.01),IL-37组低于LPS组(P<0.05)。LPS组、对照组、IL-37组小鼠心肌组织中NLRP3蛋白相对表达量分别为3.77±0.22、1.00±0.04、1.97±0.13,Caspase-1蛋白相对表达量分别为3.04±0.18、1.00±0.07、1.62±0.20,ASC蛋白相对表达量分别为2.17±0.12、1.00±0.03、0.77±0.13,小鼠心肌组织中NLRP3、Caspase-1和ASC蛋白相对表达LPS组高于对照组(P均<0.05),IL-37组低于LPS组(P均<0.05)。结论IL-37可能通过抑制NLRP3炎性小体改善脓毒症小鼠心肌�Objective To explore the effects of intraperitoneal injection of interleukin-37(IL-37)on myocardial in⁃jury in sepsis mice.Methods Thirty C57BL/6J mice were randomly divided into three groups:control group,LPS group,and IL-37 group,with 10 in each group.The mice in the LPS group were intraperitoneally injected with 20 mg/kg lipopolysaccharide(LPS),the mice in the IL-37 group were intraperitoneally injected with 20 mg/kg LPS and 1 mg/kg IL-37,and the mice in the control group were intraperitoneally injected with an equal volume of sterile normal saline.The car⁃diac function of the mice in each group was evaluated by cardiac ultrasound,and the degree of pathological damage of the myocardial tissues of the mice in each group was evaluated by HE staining.The expression levels of inflammatory factors IL-1β,IL-6 and tumor necrosis factor-α(TNF-α)in the myocardial tissues were detected by immunohistochemistry.The protein expression levels of NOD-like receptor protein 3(NLRP3)inflammasome and its related signaling pathways were an⁃alyzed by immunohistochemistry and Western blotting.Results Compared with the control group,both left ventricle ejection fraction(LVEF)and fractional shortening(FS)in the LPS group decreased(all P<0.01).Compared with LPS group,both LVEF and FS in the IL-37 group increased(all P<0.01).Compared with the control group,the myocardial tissue structure in LPS group was disordered,with the disruptive sarcolemma,congestive and oedematous myocardial interstitium.Compared with the LPS group,the heart function and myocardial histopathological injury were significantly im⁃proved in the IL-37 group.The expression levels of IL-1βwere 20.12±1.89,1.00±0.56,8.09±2.89 in the LPS group,control group and IL-37 group,the expression levels of IL-6 were 36.56±5.17,1.00±0.25,9.92±1.37,respectively,and the expression levels of TNF-αwere 20.87±6.35,1.00±0.44,and 6.23±1.29,respectively.The ex⁃pression levels of IL-1β,IL-6 and TNF-αin the myocardium in the LPS group were higher than those in the

关 键 词：脓毒症 白细胞介素-37 NLRP3炎症小体 心肌损伤 小鼠 

分 类 号：R542.[医药卫生—心血管疾病]