【摘要】 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。更多还原

【Abstract】 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 specklike 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.更多还原