肢体缺血预/后适应改善脓毒症小鼠心肌IL-6及心脏功能的作用  

Effects of limb ischemic preconditioning/postconditioning on myocardial IL-6 and cardiac function in septic mice

作　　者：陈海丽[1] 龚佳红 李旭卿 李盛村 CHEN Haili;GONG Jiahong;LI Xuqing;LI Shengcun(Rehabilitation Medical Center,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325027,China)

机构地区：[1]温州医科大学附属第二医院康复医学中心,浙江温州325027

出　　处：《温州医科大学学报》2022年第6期453-458,共6页Journal of Wenzhou Medical University

基　　金：温州市基础性科研项目(Y20211136,Y20210188);浙江省自然科学基金项目(LY22H020002)。

摘　　要：目的:探讨肢体缺血预/后适应对脓毒症心肌炎症和心脏功能的作用。方法:采用6 mg/kg脂多糖(LPS)腹腔注射诱导脓毒症小鼠模型。脓毒症小鼠分别经过单、双侧腿缺血预或后适应干预,叠加缺血预和后适应组合干预。应用qRT-PCR检测心肌中白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子(TNF-α)、Apelin和Atrogin-1 mRNA的表达。应用小动物超声仪检测小鼠心脏功能,包括分析收缩功能指标射血分数(EF)、短暂缩短率(FS)和心脏舒张功能指标E/A比值。结果:单侧腿缺血预适应和后适应均能够降低脓毒症小鼠心肌IL-6 mRNA的表达(P<0.05);预适应和后适应的组合比单独缺血预/后适应更能降低脓毒症小鼠心肌IL-6的表达(P<0.05),但与LPS组比,间隔2 h的叠加后适应进一步增加IL-6的表达(P<0.05)。LPS导致心肌中IL-1β和TNF-α表达增加,萎缩基因Atrogin-1增加,Apelin基因降低,而缺血预适应能够增强脓毒症小鼠心脏功能,降低IL-1β和TNF-α表达(P<0.05),不能够改变Atrogin-1和Apelin表达(P>0.05)。结论:缺血预适应和后适应均有效缓解LPS引起的心肌IL-6 mRNA的高表达,但后适应没有累积效应。IL-6可能是参与缺血预适应改善脓毒症小鼠心脏功能的重要因素。Objective:To investigate the effects of limb ischemic preconditioning/postconditioning on myocarditis and cardiac function in sepsis mice.Methods:Sepsis mouse model was induced by intraperitoneal injection of lipopolysaccharide(LPS)6 mg/kg.Sepsis mice were subjected to single and bilateral leg ischemic preconditioning or post adaptation intervention,or combined with ischemic preconditioning and post adaptation intervention.Proinflammatory factor interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor(TNF-α),Apelin and Atrogin-1 mRNA expression were detected by qRT-PCR.The cardiac functions of mice,including systolic function index ejection fraction(EF),transient shortening rate(FS)and diastolic function index E/A ratio,were measured by small animal ultrasound.Results:Both preconditioning and postconditioning of unilateral leg ischemia could reduce the expression of IL-6 mRNA in myocardium of septic mice(P<0.05).The combination of preconditioning and postconditioning decreased the expression of IL-6 more than ischemic preconditioning/postconditioning alone(P<0.05),but compared with LPS group,the superposition of preconditioning at an interval of 2 h further increased the expression of IL-6(P<0.05).LPS increased IL-1β,TNF-αand atrophic gene Atrogin-1 but decreased apelin gene,while ischemic preconditioning could enhance cardiac function and reduce IL-1βand TNF-αin septic mice,but did not change the expression of Atrogin-1 and Apelin(P>0.05).Conclusion:Ischemic preconditioning and postconditioning can effectively alleviate the high expression of IL-6 mRNA in myocardium induced by LPS,but postconditioning has no cumulative effect.IL-6may be an important molecule involved in ischemic preconditioning to improve cardiac function in septic mice.

关 键 词：肢体缺血预适应 肢体缺血后适应 脓毒症 心肌炎症 小鼠 

分 类 号：R49[医药卫生—康复医学]