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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Changes in PPAR gene expression and myocardial tolerance to ischaemia: relevance to pleiotropic effects of statins.
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Changes in PPAR gene expression and myocardial tolerance to ischaemia: relevance to pleiotropic effects of statins.

机译：PPAR基因表达和心肌耐受对缺血性的变化：与他汀类药物脂肪效应的相关性。

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Peroxisome proliferator-activated receptors (PPAR), which are key transcriptional regulators of lipid metabolism and energy production, have been suggested to play an important role in myocardial ischaemia-reperfusion (I/R) injury. Their role in cardioprotection, however, is not yet fully elucidated. Statins have shown beneficial effects on I/R damage beyond lipid lowering, and some of their cardioprotective cholesterol-independent effects may be related to the regulation of PPAR. To clarify this issue, we explored a potential link between a response to I/R and changes in cardiac PPARalpha protein and gene expression in simvastatin-treated normocholesterolaemic rats. After 5 days of treatment with simvastatin (10 mg/kg per day, p.o.), Langendorff-perfused hearts were subjected to 30 min regional ischaemia (occlusion of the left anterior descending coronary artery) or global ischaemia and 2 h reperfusion for the evaluation of the infarct size (triphenyltetrazolium chloride and planimetry; as percentage of risk area), ischaemic arrhythmias, and postischaemic contractile recovery. Baseline PPARalpha mRNA and protein levels were increased by 3-fold and 2-fold, respectively, in simvastatin-treated hearts compared with the untreated controls. Simvastatin-treated hearts exhibited smaller size of infarction (11.5% +/- 0.4% vs. 33.7% +/- 4% in controls; p < 0.01), improved postischaemic contractile recovery, and lower severity of arrhythmias during ischaemia and early reperfusion. Enhanced resistance to I/R injury was associated with preservation of mRNA and protein levels of PPARalpha in contrast to their marked downregulation in controls. In conclusion, statin-induced changes in the expression of PPARalpha may contribute to attenuation of myocardial I/R injury and thus suggest the involvement of cardioprotective mechanisms independent of inhibition of HMG-CoA reductase.
机译：已经提出了作为脂质代谢和能量产生的关键转录调节剂的过氧化物酶体增殖物激活的受体（PPAR）在心肌缺血再灌注（I / R）损伤中起重要作用。然而，它们在心脏保护中的作用尚未完全阐明。他汀类药物对脂质降低的I / R损伤有益效果，其一些心脏保护胆固醇无关的效果可能与PPAR的调节有关。为了澄清这个问题，我们探讨了对I / R的反应和心脏杀螨蛋白蛋白质和基因表达的反应之间的潜在联系，并在辛伐他汀治疗的炔醇糖醇类大鼠中的基因表达。在用辛伐他汀治疗5天后（每天10毫克/千克）后，Langendorff-灌注的心脏受到30分钟的区域缺血（左前期下降冠状动脉的闭塞）或全球性缺血和2小时再灌注评估梗塞大小（三苯基四唑氯化氢和平面图;作为风险区域的百分比），缺血性心律失常和后期患有接触恢复。与未处理的对照相比，基线Pparalpha mRNA和蛋白水平分别在辛伐他汀处理的心中分别增加3倍和2倍。辛伐他汀治疗的心脏表现出较小的梗塞（11.5％+/- 0.4％，对照组11.7％+/- 4％; P <0.01），改善后性接收恢复，以及在缺血和早期再灌注期间的心律失常严重程度。与对照中标记的下调相比，增强对I / R损伤的抗mRNA和蛋白质水平的保存有关。总之，杀螨蛋白酶诱导的杀螨物表达的变化可能有助于衰减心肌I / R损伤，从而表明心脏保护机制与HMG-COA还原酶的抑制无关。

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