线粒体ATP敏感性钾通道在桑色素对离体大鼠心脏保护作用中的可能作用

心肌缺血时，心肌细胞缺氧通过开放线粒体通透性转换孔(MPTP)引起pH、离子紊乱和细胞死亡。考虑到线粒体ATP依赖性钾通道(mt-K)对这些毛孔的抑制作用和桑色素的抗缺血作用，我们推测mt-K可能通过激活mt-K和抗氧化作用发挥其积极作用。 

用富含桑色素(0.25，0.5，1 mg/L)或5-羟基癸酸(5-HD，mt-K阻滞剂；100minμM)的Krebs-Henseleit液灌流大鼠离体心脏，根据需要在开始区域缺血前5min灌流，直至再灌注期前10min。分别用Krebs-Henseleit液灌流60min和120min进行生化评价(乳酸脱氢酶和丙二醛水平)或评价心肌梗死范围。实验期间记录血流动力学功能并测定心律失常。

我们的发现表明，桑色素减少了梗死面积。此外，桑色素灌流还能显著防止缺血时丙二醛的过量生成。在缺血期和再灌注期，总的室性异位搏动与丙二醛水平有相同的显著变化。桑色素也能相对改善缺血所致的血流动力学障碍。同时灌流5-HD可逆转桑色素的上述保护作用。

桑色素通过抗氧化作用对缺血心脏有保护作用。这也表明桑色素的心脏保护作用与mt-K之间存在联系。然而，还需要更多的研究来证明这一初步假设。

Aims: During heart ischemia, the lack of oxygen in the myocardial cellscauses pH and ion disturbances andcell death through opening mitochondrial permeability transition pores (mPTP). Considering the inhibitory effects of mitochondrial ATP-dependent potassium channels(mt-KATP) on these pores and anti-ischemic effects of morin, we hypothesized that it may exert its positive effects via activating mt-KATP as well as its anti-oxidative effects.

Main methods: Isolated rat hearts were perfused by Krebs-Henseleit solution enriched with the morin (0.25, 0.5 and 1mg/L) or 5-hydroxydecanoate (5-HD, a mt-KATPblocker;100 μM)or bothas needed5 minutes before starting regional ischemia till the first ten minutes of the reperfusion period.The reperfusionwas developed with Krebs-Henseleit solution 60 or 120 minutes respectively for biochemical evaluations(lactate dehydrogenase and malondialdehydelevel)or the assessment of myocardial infarct size.During the experiments,hemodynamic functions were recorded and cardiac arrhythmias were determined.

Key findings: Our findings demonstrated that morinreduced the infarctsize. Also, morinperfusion could remarkably prevent the malondialdehydeover-productionduring ischemia.Total ventricular ectopic beats had the same significant changes as the malondialdehydelevel, in both ischemia and reperfusion phases. Morincouldalsorelatively improve the ischemia-induced hemodynamic dysfunction. All mentioned protective effects of morinwere reversed by concomitant perfusion of 5-HD.

Significance: Morinhasprotective effects against ischemic hearts through anti-oxidative effects. It also suggests a link between the cardioprotective effects of morin and mt-KATP.However, additional studies are requiredto prove this preliminary hypothesis.