Second University Department of Cardiology, Medical School, Attikon General Hospital, University of Athens, Rimini 1, 124 62 Athens, Greece.
Basic Res Cardiol. 2010 Mar;105(2):193-203. doi: 10.1007/s00395-009-0078-3.
Postconditioning (POC) reduces lethal reperfusion injury under normal conditions, but its effectiveness under certain pathological states is in dispute. In the present study, we sought to determine the effect of chronic simvastatin treatment in hyperlipidemic animals with or without POC. Anesthetized rabbits were randomized into eight groups, as follows, and were subjected to 30-min myocardial ischemia followed by 3-h reperfusion. Normally fed animals: a Control group with no additional intervention, a Sim group treated with simvastatin for 3 weeks at a dose of 3 mg kg(-1), a POC group subjected to POC with eight cycles of 30-s ischemia/reperfusion, a Sim-POC group treated with simvastatin, and POC. Cholesterol fed (6 weeks) animals: a Chol group with no additional interventions, a Chol-Sim group treated with simvastatin for 3 weeks, a Chol-POC group subjected to POC, and a Chol-Sim-POC group treated with simvastatin and POC. Infarct size and plasma levels of malondialdehyde (MDA), nitrotyrosine (NT), NOx, total cholesterol, and LDL were evaluated. In a second series of experiments, heart tissue samples were taken for MDA, NT, and NOx assessment. Infarct size, circulating MDA, NT, NOx and cardiac MDA, NT, and NOx levels declined in POC and all Sim groups compared with Control, Chol, and Chol-POC (p < 0.05). Simvastatin also reduced total cholesterol and LDL plasma levels. In conclusion, a 3-week simvastatin treatment limits the infarct size and attenuates the oxidative and nitrosative stress both in normo- and in hyper-cholesterolemic rabbits subjected to ischemia-reperfusion irrespective of the presence of POC, while POC is effective only in normocholesterolemic animals.
预处理（POC）可减少正常情况下致命再灌注损伤，但在某些病理状态下的效果存在争议。在本研究中，我们旨在确定在高脂血症动物中，是否存在 POC 以及是否存在慢性辛伐他汀治疗的效果。麻醉兔随机分为 8 组，如下所述，并进行 30 分钟心肌缺血，随后进行 3 小时再灌注。正常喂养的动物：a 无其他干预的对照组，b 用辛伐他汀治疗 3 周，剂量为 3mg/kg 的 Sim 组，c 进行 8 个周期 30 秒缺血/再灌注的 POC 组，d 用辛伐他汀治疗的 Sim-POC 组。胆固醇喂养（6 周）的动物：a 无其他干预的 Chol 组，b 用辛伐他汀治疗 3 周的 Chol-Sim 组，c 进行 POC 的 Chol-POC 组，d 用辛伐他汀和 POC 治疗的 Chol-Sim-POC 组。评估梗塞面积和丙二醛（MDA）、硝基酪氨酸（NT）、NOx、总胆固醇和 LDL 血浆水平。在第二个实验系列中，心脏组织样本用于 MDA、NT 和 NOx 评估。与 Control、Chol 和 Chol-POC 相比，POC 和所有 Sim 组的梗塞面积、循环 MDA、NT、NOx 和心脏 MDA、NT 和 NOx 水平均降低（p < 0.05）。辛伐他汀还降低了总胆固醇和 LDL 血浆水平。总之，3 周的辛伐他汀治疗可限制梗塞面积，并减轻氧化和硝化应激，无论缺血再灌注的动物是否存在 POC，而 POC 仅在正常胆固醇血症的动物中有效。
