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目的:观察三磷酸腺苷(ATP)和腺苷A2a受体激动剂CGS-21680后处理对心肌缺血/再灌注损伤(MIRI)的影响,并探讨其作用的机制。方法:健康新西兰大白兔60只,随机分成5组(n=12):即对照组、缺血/再灌注(I/R)组、缺血后处理(IPO)组、ATP组及CGS-21680组。建立兔心肌I/R模型,于再灌注末颈动脉取血,应用放射免疫测定法(RIA)测定血清中白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的含量;用TUNEL法检测心肌细胞的凋亡;实时荧光定量RT-PCR检测各组心肌组织中IL-1βmRNA和TNF-αmRNA的表达。结果:①与I/R组比较,IPO组、ATP组和CGS21680组血清IL-1β、TNF-α的含量明显降低(P<0.01);而3组组间相比较无显著差异。②IPO组、ATP组和CGS-21680组的细胞凋亡指数(AI)较I/R组明显降低,心肌组织损伤也显著减轻。同时,IPO组、ATP组和CGS-21680组IL-1β、TNF-αmRNA的表达明显低于I/R组;但3组间比较无显著差异。细胞凋亡和IL-1β、TNF-αmRNA的表达之间呈正相关(分别为r=0.91和r=0.93,P<0.05)。结论:ATP后处理可减轻MIRI,其作用机制可能与抑制炎症反应,减少细胞凋亡有关。
Objective: To observe the effects of adenosine triphosphate (A2) and adenosine A2a receptor agonist CGS-21680 on myocardial ischemia / reperfusion injury (MIRI) and to explore its mechanism. Methods: Sixty New Zealand white rabbits were randomly divided into five groups (n = 12): control group, ischemia / reperfusion group, IPO group, ATP group and CGS-21680 group. Rabbit myocardium I / R model was established and blood was taken from the carotid artery at the end of reperfusion. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum were determined by radioimmunoassay (RIA) . The apoptosis of myocardial cells was detected by TUNEL method. The expression of IL-1βmRNA and TNF-αmRNA in myocardium were detected by real-time fluorescent quantitative RT-PCR. Results: ①Compared with I / R group, the levels of IL-1β and TNF-α in IPO group, ATP group and CGS21680 group were significantly decreased (P <0.01); while there was no significant difference between the three groups. (2) The apoptosis index (AI) of the IPO group, the ATP group and the CGS-21680 group was significantly lower than that of the I / R group and the damage of myocardial tissue was also remarkably reduced. At the same time, the expression of IL-1β, TNF-αmRNA in IPO group, ATP group and CGS-21680 group was significantly lower than that in I / R group; however, there was no significant difference among the three groups. There was a positive correlation between apoptosis and expression of IL-1β and TNF-αmRNA (r = 0.91 and r = 0.93, P <0.05 respectively). Conclusion: ATP posttreatment can reduce MIRI, and its mechanism may be related to inhibition of inflammatory reaction and decrease of apoptosis.