罗格列酮不同时程给药在心肌缺血再灌注中的保护作用

The Protective Effect of Peroxisome Proliferators-activeted Receptor-γ-agonist,Rosiglitazone by Different Times after Cardiac Ischemia Reperfusion

目的:观察过氧化物酶增殖物激活型受体γ(PPARγ)激动剂罗格列酮不同时程给药后对小鼠心肌缺血再灌注损伤(I/R)的保护作用,并对其机制进行初步探讨。方法:制备鼠冠状动脉阻塞再灌注模型,罗格列酮6 mg/kg的剂量,分别于不同时间点即:术前1 h、再灌注时、再灌注后1 h、再灌注后2 h给予腹腔注射,通过逆转录聚合酶链反应(RT-PCR)、蛋白免疫印迹法(Western-Blot)观察细胞间黏附分子(ICAM-1)、白细胞介素-1(IL-1)β蛋白表达以及mRNA水平合成情况。结果:罗格列酮处理组均可减轻受损心肌组织的病理变化,抑制ICAM-1、IL-1β蛋白表达及其mRNA合成。但是以术前1 h给药效果最显著,且表现随时间的延长有递减的趋势。结论:罗格列酮对小鼠心肌缺血再灌注损伤有一定的保护作用,以超早期用药效果显著。其作用机制与抑制缺血后炎症因子表达,减轻缺血后炎症有关。

Objective： To observe the protective effect of peroxisome proliferators - active - receptor - γ agonist, rosiglitazone, injected intraperitoneally at different times on mice model of cardiac ischemia reperfusion. Methods： Adult male mice underwent coronary occlusion reperfusion received rosiglitazone of 6 mg/kg at 1 h before coronary occlusion, when reperfusion after 2 h coro- nary occlusion, 1 h after reperfusion,2 h after reperfusion. The contents of ICAM - 1 ,IL - 1β were determined by Western - Blot and their mRNA levels were determined by reahime RT - PCR. Results： All groups that received rosiglitazone decreased infart area, pro- tected myocardium in mice. PPAR agonist also significantly reduced ICAM- 1 ,IL- 1β content and their mRNA synthase.Group of 1 h before coronary occlusion has significantly myocardial preservation than the others. Conclusion： The present study provides the in vivo evidence that PPAR agonist protects heart against cardiac ischaemia - reperfusion injury by anti - inflammatory.