大鼠缺血再灌注心肌TLR4、TNF-α表达变化及其关系研究.docVIP

大鼠缺血再灌注心肌TLR4、TNF-α、NF-κB表达及其关系的研究 刘冬云1 刘坤申2 摘要：目的 研究缺血再灌注大鼠心肌TLR-4、TNF-α和NF-κB的表达及相互关系。方法 建立大鼠缺血再灌注模型，大鼠随机分为假手术组、缺血组、再灌注30min组、再灌注60min组、再灌注90min组。以RT-PCR法检测心肌中TLR4及TNF-α mRNA的表达。结果 各种心肌中均检测到TLR4的表达，缺血及再灌注后TLR-4mRNA含量显著增加，随着再灌注时间延长，TLR-4mRNA含量增加更为显著。缺血组与假手术组TNF-α mRNA表达没有显著差异，而再灌注后表达显著增加，随再灌注时间延长，TNF-α mRNA含量继续增加更为明显。缺血及再灌注后心肌NF-κB mRNA表达增加，随再灌注时间延长，NF-κB mRNA含量继续增加，且具统计学意义。TLR-4表达增加时TNF-α和NF-κB表达也增加，三者有一定相关性。结论 心肌缺血再灌注损伤使TLR-4、TNF-α表达增高，阻断TLR-4可能有助于减轻缺血再灌注所致心肌损伤，并抑制急性炎症反应的发生。 关键词：　缺血再灌注损伤　心肌Toll样受体4 TNF-α NF-κB Expression of TLR-4 、TNF-α and NF-κB In rat cardial muscles during ischemia-reperfusion LIU Dong-yun1 LIU Kun-shen2 (1Emergency Department, Bethune International Peace hospital of Chinese PLA, Cardialogy Deparment, the First Clinic Hospital of Hebei Medical Univrersity ,050082 Shijiazhuang, Hebei China) Abstract: Objective To investigate the expression of TLR-4 、TNF-α and NF-κB In rat cardial muscles during ischemia reperfusion. Methods Twenty-five female SD rats were randomly divided into sham operation group (n=5), ischemia group(n=5) ,ischemia reperfusion 30min group(n=5), ischemia reperfusion 60min group(n=5), ischemia reperfusion 90min group(n=5), Expression level of TLR4 、TNF-α were measured by RT-PCR. Result The expression level of TLR4 、TNF-α and NF- κB significantly increased after ischemia- reperfusion.,there are positive correlation among them .Conclusiongs These data suggest that myocardial ischemia- reperfusion can result in intensive activation of TLR-4 、TNF-α .and NF- κB. Treatment with inhibitors to TLR4 may be benefit for attenuation of myocardial injury induced by ischemia- reperfusion and subsequent acute inflammatory response. Key words: TLR-4; ischemia- reperfusion; NF- κB; TNF- α 心肌缺血再灌注损伤（Myocardium ischemia-reperfusion injury, MIRI）是心肺复苏、心肌梗塞溶栓和介入治疗、以及心脏移植中的重要病理生理过程。局部及全身炎症是缺血再灌注损伤的特征，但激发炎症的具体过程未完全阐明。由于Tool样受体（TLR-4）在识别细菌LPS及介导的炎症反应信号转导中的重要作用[1]，其在心肌缺血再灌注损伤中的作用也越来越多的引起关注。目前