摘要
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。
AIM:To explore the effects and mechanism of adenosine triphosphate and adenosine receptor agonist pharmacological postconditioning on myocardial ischemia/reperfusion (I/R) injury in rabbits. METHODS: Sixty New Zealand white male rabbits were randomly divided into five groups (n=12 each): control group, I/R group, IPO group, ATP group and CGS-21680 group. The model of myocardial ischemia/reperfusion was established and the concentrations of IL-1β and TNF-α were detected by radioimmunoassay at the end of 3 h reperfusion. TUNEL method was employed to detect apoptotic changes and real-time quantitative RT-PCR was used to detect the expression of IL-1β and TNF-α mRNA in myocardial tissue. RESULTS: Compared with those in I/R group, the concentrations of IL-1β and TNF-α markedly decreased in IPO group, ATP group and CGS-21680 group. However, the differences of three groups were not significant. Compared with those in I/R group, the apoptosis indexes significantly decreased in IPO group, ATP group and CGS-21680 group. The expressions of IL-1β and TNF-α mRNA decreased obviously in IPO group, ATP group and CGS-21680 group. A positive correlation was found between apoptosis and the expressions of IL-1β and TNF-α mRNA (r=0.91, r=0.93; P〈0.05). CONCLUSION: ATP-postconditioning attenuates myocardial ischemia/reperfusion injury, possibly by inhibiting the effect of inflammation and decreasing myocardial apoptosis.
出处
《心脏杂志》
CAS
2011年第5期594-597,共4页
Chinese Heart Journal