腺苷抑制NF-κB在肺炎大鼠心肌损伤中的作用

Effect of adenosine on NF-κB activity in experimental rats with pneumonia

目的 :观察金葡菌感染大鼠肺炎时心肌组织核因子 - κB(NF- κB)的表达 ,以及不同剂量腺苷对其影响 ,以进一步探讨重症肺炎并发心肌损害的机制和腺苷治疗的疗效及理论基础。方法 :SD大鼠 5 0只被随机分为 5组 ,分别为正常对照组、肺炎组和腺苷治疗 A、B、C组。金葡菌经气管插管注入复制肺炎大鼠模型 ,于注菌后第 2、3、4天静脉点滴腺苷治疗 ,每天 90 min,剂量分别为 5 0、10 0、15 0μg· kg- 1 · min- 1 。第 5天处死大鼠 ,立即取心脏液氮保存 ,心肌组织用于病理检测 ,提取核蛋白用 EMSA方法检测 NF- κB活性。结果 :1心肌病理组织检查示肺炎组病变明显 ,与对照组比较差异显著 (P<0 .0 1) ,腺苷有保护心肌作用 (P<0 .0 1) ,并呈剂量依赖性 ;2肺炎组 NF- κB活性较对照组显著增高 (P<0 .0 1) ,腺苷呈剂量依赖性地抑制心肌 NF-κB活性 (P<0 .0 1)。结论 :本研究证实金葡菌感染大鼠肺炎可致心肌损害 ,NF- κB参与心肌损伤的发生和发展。外源性腺苷可通过抑制 NF- κB活性 ,从而有利于炎症的减轻和保护心肌 ,此为临床应用腺苷治疗重症肺炎并发心肌损害和心功能不全提供了理论依据。

AIM:To further investigate the role of NF-κB in the mechanism of myocardium injury casused by infectious pneumonia and the therapeutic effects of exogenous adenosine by observing the activity of NF-κB in injured myocardium and the effects of different dosages of adenosine on NF-κB activity. METHODS:Fifty rats were divided into five experimental groups at random,each group had 10 rats. The model of pneumonia was induced by the injection of staphylococcus aureus into the windpipe of rats. Adenosine-treated rats(A?B and C group) received daily injection of adenosine at different dosages (50?100 and 150 μg·kg -1·min -1) for 3 days. All rats were killed on the fifth day. Myocardial tissues were preserved in liguid nitrogen for examination. Pathological exa mination of myocardium were done and NF-κB activity was detected by electrophoretic mobility shift assay (EMSA). RESULTS:①Significant increase of NF-κB activity was observed in myocardium of pneumonic rats when compared with control group (P<0.01,respectively). The increased levels of NF-κB activity were positively correlated with pathological changes in injuried myocardium(P<0.01,respectively); ②NF-κB activity were dosage-dependently decreased in adenosine-treated rats(B?C groups) when compared with pneumonia group(P<0.01,respectively), but no significant change in A group(P>05). CONCLUSION: According to our finding, NF-κB may be involved in the development of myocardial injury in rats with pneumonia. Exogenous adenosine can inhibits inflammation by down-regulation NF-κB activity, and protect injured myocardium in rat with pneumonia. Our findings provide novel therapeutic evidence of adenosine in myocardial injury induced by pneumonia in clinic.