首页|高强度间歇运动通过调控NLRP3炎症小体和M1巨噬细胞极化改善脓毒症心肌损伤

高强度间歇运动通过调控NLRP3炎症小体和M1巨噬细胞极化改善脓毒症心肌损伤

扫码查看
目的 探讨高强度间歇运动(HIIT)对脂多糖(LPS)诱导的小鼠脓毒症心肌损伤的影响,以及NLRP3炎症小体和巨噬细胞M1型极化在其中的作用机制.方法 取 C57BL/6雄性小鼠随机分为4组:对照(CON)组、LPS(L)组、高强度间歇运动+注射生理盐水(E)组和高强度间歇运动+注射LPS(EL)组.6周HIIT运动干预后腹腔注射LPS,12 h后采用超声心动图测量心功能指标;苏木素-伊红(HE)染色评价心肌形态和病理特征,评估心肌损伤分数;酶联免疫吸附实验(ELISA)测试心肌损伤指标(AST、CK-MB、LDH)含量;使用RT-PCR测试心脏组织中NLRP3炎症小体(NLRP3、Caspase-1)、心房钠尿肽(ANP)、脑钠肽(BNP)、髓过氧化物酶(MPO)和巨噬细胞M1相关炎症因子(IL-1β、TNF-α、IL-6)mRNA的相对表达;Western blot 检测心脏组织诱导型一氧化氮合酶(iNOS)、凋亡相关斑点样蛋白(ASC)蛋白表达;免疫荧光染色检测心脏NLRP3炎症小体(NLRP3、ASC、IL-18)、iNOS蛋白表达.结果 与CON组比较,LPS 组小鼠体质量变化明显,EF、FS下降明显,LVESD、LVEDD明显上升,心肌组织可见明显病理损伤,心肌损伤分数明显升高,血清心肌损伤指标水平显著升高,BNP、MPO、NLRP3炎症小体、iNOS、IL-1β、IL-6和TNF-α表达水平显著升高(P<0.05);与LPS组比较,HIIT组明显改善EF、FS、LVESD、LVEDD变化,心肌组织病理损伤缓解、心肌损伤分数降低,LDH水平降低,心肌组织BNP、MPO、NLRP3 炎症小体(NLRP3、ASC)、iNOS和相关炎症因子表达明显降低(P<0.05).结论 6周的HIIT可抑制LPS诱导的NLRP3炎症小体活化,抑制巨噬细胞 M1型极化,进而防治脓毒症心肌损伤,NLRP3炎症小体和巨噬细胞M1极化可能是HIIT发挥心肌保护作用的机制.
High-intensity interval training alleviates sepsis-induced myocardial injury by regulating NLRP3 inflammasome and M1 macrophage polarization
The aim of this study was to investigate the effects of high-intensity interval training(HIIT)on lipopolysaccharide(LPS)-induced septic myocardial injury in mice and the roles of NLRP3 inflammasome and macrophage M1 polarization in the process.C57BL/6 male mice were randomly divided into 4 groups:control(CON)group,LPS(L)group,HIIT+saline injection(E)group,and HIIT+LPS(EL)group.Six weeks of HIIT intervention was followed by intraperitoneal injection of LPS,and cardiac function indexes were measured by echocardiography 12 hours post the injection.Hematoxylin-eosin(HE)staining was used to evaluate the morphology and pathological characteristics of myocardium for assessing myocardial damage score;enzyme-linked immunosorbent assay(ELISA)was used to test the content of myocardial damage indicators(AST,CK-MB,LDH);RT-PCR was used to detect the relative mRNA levels of NLRP3 inflammasome(NLRP3,Caspase-1),atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),myeloperoxidase(MPO)and macrophage M1-associated inflammasome factors(IL-1β,TNF-α,IL-6);Western blot was applied to measure the protein expression of inducible nitric oxide synthase(iNOS)and apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)in cardiac tissues;immunofluorescence staining was used to detect the protein expression of NLRP3 inflammasome,ASC,IL-18 and iNOS.Compared with the CON group,mice in the LPS group showed obvious decrease in body weight,a significant decrease in EF and FS,a significant increase in LVESD and LVEDD,obvious pathological damage in myocardial tissue,a significant increase in myocardial damage fraction,a significant increase in serum myocardial damage indexes,and a significant increase in the expression levels of BNP,MPO,NLRP3 inflammasome,iNOS,IL-1β,IL-6 and TNF-α.HIIT treatment could reverse these changes mentioned above in model mice.In conclusion,6 weeks of HIIT inhibits the activation of LPS-induced NLRP3 inflammasome and suppressed macrophage M1-type polarization,thereby combating septic myocardial injury.

High intensity interval trainingMacrophage polarizationNLRP3 inflammasomeSepsis

张铭宸、李婷婷、张慧、陈明华、段玉双、王孝文、孙忠广

展开 >

261053 潍坊,山东第二医科大学康复医学院

215000 苏州,苏州大学附属第四医院康复医学科

250132 济南,山东省公共卫生临床中心康复医学科

高强度间歇运动 巨噬细胞极化 NLRP3炎症小体 脓毒症

山东省自然科学基金青年项目潍坊市科技发展计划项目山东第二医科大学大学生创新创业训练计划

ZR2022QH0942021YX083X2024339

2024

免疫学杂志
第三军医大学,中国免疫学会

免疫学杂志

CSTPCD
影响因子:0.704
ISSN:1000-8861
年,卷(期):2024.40(4)