摘要
目的研究Janus激酶/信号转导和转录激活子(januskinase/signaltransducerandactivatoroftranscription,JAK/STAT)通路对缺血再灌注损伤所至大鼠心肌组织NF-κB和TNF-α表达的影响。方法采用离体工作心脏灌注模型,大鼠随机分为正常对照组、缺血再灌注组、JAK抑制剂-AG490治疗组和STAT抑制剂—RMP治疗组。采用Western印迹法测定心肌NF-κB活性,ELISA检测试剂盒检测TNF-α蛋白含量。结果与正常对照组相比,心肌组织NF-κB活性和TNF-α含量在缺血再灌注后有显著性增加(P<0.05)。AG490及RMP处理后,NF-κB活性和TNF-α含量与缺血再灌注组相比有明显下降(P<0.05);与正常对照组相比较,仅有少许升高,差异无显著性(P>0.05)。NF-κB活性增加时TNF-α含量也相应升高,反之亦相同,两者呈一定程度的正相关。结论心肌缺血再灌注损伤使NF-κB和TNF-α表达明显升高,抑制JAK/STAT通路的活化可下调心肌组织NF-κB和TNF-α的表达,这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。
[Objective ] To investigate the effect of janus kinase/signal transducer and activator of transcription （JAK/STAT） pathway in mediating activity of NF-kB and level of TNF-α during ischemia-repeffusion in rat cardial muscles. [Methods] Using isolated rat heart model, 24 male SD rats were randomly divided into normal control group （n=6）, ischemia-repeffusion group （n=6）, AG490 treatment group （n=6）, RMP treatment group （n=6）. The NF-kB in nuclear was extracted and measured by western blot analysis. TNF-α level in the myocardium were measured using enzyme-linked immunosorbent assay[ELISA）, system. [Results] NF-kB activity in nuclear significantly increased after ischemia-repeffusion and TNF-α levels had the same change. Treatment with AG490 or RMP significandy inhibited NF-kB activity in nuclear, and concomitantly decreased the level of TNF-α in the myocardium. [Conclusions] These data suggest that myocardial ischemia-repeffusion can result in intensive activation of NF-kB and TNF-α. Early treatment with inhibitors to JAK/STAT pathway may be benefit for attenuation of myocardial injury induced by iscbemia-repeffusion and subsequent acute inflammatory response.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2006年第7期985-987,991,共4页
China Journal of Modern Medicine
