反复缺血预适应对心肌缺血再灌注损伤大鼠TLR4和致炎细胞因子TNF-α、IL-1β的影响  

Repeated ischemic preconditioning attenuates rat myocardial ischemical reperfusion injury through down-regulating TLR4 and decreasing peripheral TNF-α and IL-1β levels

作　　者：罗永金[1] 杨双强[1] 杨庆军[2] 

机构地区：[1]重庆医科大学附属第一医院胸外科,重庆400016 [2]重庆市中山医院心外科,重庆400013

出　　处：《第三军医大学学报》2009年第23期2347-2350,共4页Journal of Third Military Medical University

摘　　要：目的探讨缺血预适应(ischemic preconditioning)对心肌缺血再灌注损伤(myocardial ischemical reperfusioninjury,MI/RI)大鼠的具体保护机制。方法18只雄性SD大鼠(350～400g)被随机分为假手术对照组(Sham组)、缺血再灌注组(IR组)和缺血预适应组(IP组),每组6只大鼠。成功制备上述3种动物模型后,收集动物外周血和切取病变心肌组织。采用酶标记免疫吸附法(enzyme-labeled immunosorbent assay,Elisa)测定动物外周血血清中致炎细胞因子TNF-α、IL-1β的含量;分别采用RT-PCR和Western blot技术检测大鼠病变心肌组织中Toll样受体4(Toll-like receptor4,TLR4)在转录水平和蛋白水平上的变化。结果相对于IR组,缺血预适应可有效降低心肌缺血再灌注损伤大鼠血清中致炎细胞因子TNF-α、IL-1β的水平(P<0.01);同时,相对于IR组,PC组中TLR4mRNA和蛋白水平明显下调(P<0.01)。结论缺血预适应作为心肌缺血再灌注损伤的内源性保护措施,其具体作用机制可能与其降低心肌中TLR4和外周致炎细胞因子TNF-α、IL-1β的表达有密切联系。Objective To investigate the protective mechanism of ischemic preconditioning for myocardial ischemic reperfusion injury （MI/RI） rats. Methods Eighteen male Sprague - Dawley （SD） rats were randomly separated into Sham operation, ischemic reperfusion （IR） and ischemic preconditioning （IP） groups （6 rats in each group）. Peripheral blood and cardiac muscle were collected after the establishment of the above 3 animal models. ELISA was employed to determine proinflammatory cytokines TNF-α and IL-1β production in sera of these animals. RT-PCR and Western blot analysis was used to assay the transcriptional level and protein level of Toll-like receptor 4 （TLR4） in cardiac muscle tissue with pathological change, respectively. Results Compared with IR group, ischemic preconditioning effectively decreased the expression levels of TNF-α and IL-1β in sera of rats in IP group （P 〈0.01 ）. Meanwhile, TLR4 mRNA and protein levels were down-regulated （P 〈 0.01, 0.05, respectively）. Conclusion As an endogenous protective measure, ischemic precondi- tioning may protect cardiac muscle form MI/RI through down-regulating expressions levels of TLR4 and decrea- sing peripheral levels of proinflammatory cytokines such as TNF-α and IL-1β.

关 键 词：心肌缺血再灌注损伤 缺血预适应 TLR4 TNF-α IL-1Β 

分 类 号：R392.11[医药卫生—免疫学] R364.12[医药卫生—基础医学]