腺苷A_1受体介导的预处理延迟效应对低温心麻液保护作用的影响

Effect of Delayed Action of Preconditioning induced by Adenosine A_1 Receptor Analogue on Myocardial Protection of Hypothermial Cardioplegia Solution in Rats

目的利用大鼠离体心脏缺血-再灌模型,了解腺苷A1受体介导的大鼠心脏预处理延迟效应对低温心麻液保护作用的影响以及与肿瘤坏死因子表达的关系。方法雄性Wistar大鼠随机分为正常对照组(Z)、缺血对照组(C)、CCPA预处理组(A)。离体心脏低温缺血180min、复灌60min。观察左室压力变化最大速率恢复率、心肌同功酶漏出量,并以免疫组织化学、原位杂交或逆转录、PCR技术观察TNF-αmRNA和蛋白质的表达水平。结果A组左室压力变化最大速率恢复率明显高于C组(P<0.05),心肌同功酶漏出量明显低于C组(P<0.05)。A组TNF-α表达水平虽然高于Z组,但明显低于C组,差异有显著性(P<0.01)。结论腺苷A1受体介导的预处理延迟效应能增强低温心麻液的保护效果,进一步减轻心肌缺血-再灌注损伤;同时下调心脏TNF-α的表达可能是其机制之一。

Objectives To explore the effect of delayed action of preconditioning induced by adenosine A1 receptor Analogue on the my ocarolial protection of the hypothermial caidioplegia solution, and relationship between it and TNF - α expression level. Methods Twenty - five Male Wistar rats were randomly divided into three groups,i.e.normal controd group,ischemia control group,and group of delayed preconditioning with CCPA. Isolated rat hearts were subjected to 180 minutes hypothermia ischemia and 60 minutes warm reperfusion. The ± dp/dtmax of left ventricle and CK- MB leakage were observed.TNF-α expression was determined by immunohistochemistry,in situ hybridization and RT- PCR.Results The recovery rate of ± dp/dtmax in preconditioning group was significantly higher than that in ischemia control group ( P < 0.05) ,while CK - MB leakage was significantly fewer than that in ischemia control group ( P < 0.05) .TNF-α expression level in the preconditioning group as significantly lower than that in ischemia control group ( P < 0.01) . Conclusions Preconditioning with adenosine A1 receptor Analogue,CCPA can produce delayed effect of hypothermial cardioplegial solution on myocardianal protection against ischemic- reperfusion injury, and decrease in expression of TNF -α. The decrease in the expression of TNF - α, which may be one of mechanisms of delayed myocardial protection of the preconditioning.