Cardiomyocyte apoptosis induced in ischemia-reperfusion Langendorff preparation and the development of new cardiac drug.

1.缺血-再灌注Langendorff心脏的细胞凋亡不是单独由缺氧引起的，而是在缺氧或缺氧的情况下，葡萄糖的剥夺主要通过细胞凋亡诱导心肌细胞死亡。缺氧和缺氧均使细胞凋亡损伤在形态学上加重。在缺氧或缺氧的情况下，葡萄糖剥夺与ATPi含量下降和细胞内酸中毒同时发生（Tong et al., 2001）。Na^+H^+交换（NHE）抑制剂SM-198110 （Cl -结构）和SM-197378 （F -结构）对Langendorff心脏缺血/再灌注损伤的LVDP（约100% vs.无药心脏39%）有保护作用。在灌注的fura-2线粒体制备中，两种NHE抑制剂均抑制了酸化后线粒体Ca^<2+>和类似于全脑缺血后再灌注后的Ca变化。SM-198110对活性氧自由基无直接猝灭作用，SM-197378对活性氧自由基无直接猝灭作用。sm -197278处理的心脏长时间缺血再灌注后的凋亡细胞数量明显少于sm -198110处理的心脏，与caspase-3活性水平一致（Hotta et al., 2003）。3.5- ht_ <1A>或环二肽（啤酒或谷子白兰地蒸馏渣）对Alp含量较高的缺血再灌注损伤有有益作用。通过酸化或灌注液Ca^<2+>含量来猝灭活性氧自由基和抑制线粒体Ca^<2+>。这些化合物还能抑制凋亡细胞和caspase-3的活性水平（Huang and Akutagawa et al., 2004）。白术皂苷（10^<->3 M）打开线粒体通透性过渡孔（MPTP），也通过酸化或Ca^<2+>含量变化引起线粒体Ca^<2+>的类似增加。在Langendorff缺血/再灌注损伤模型中，抑制MPTP的环孢素A （10^<-4> M）或许多促进LVDP良好恢复的药物也受到抑制，但不抑制MPTP的FK506 (10^<-4> M) （Hotta et al., 2004）。少

1.Apoptosis in the ischemia-reperfusion Langendorff hearts was not induced by oxygen-deprivation alone, but the deprivation of glucose that induced myocardial cell death mainly by apoptosis in the presence or absence of oxygen. The deprivation of both oxygen and glucose exaggerated the apoptotic lesion morphologically. Glucose deprivation coincided with the decrease in ATPi content and intracellular acidosis in the presence or absence of oxygen (Tong et al., 2001).2.The protective effects of Na^+H^+ exchange (NHE) inhibitors SM-198110 (Cl in structure) and SM-197378 (F in structure) had beneficial effects of LVDP (about 100% vs. drug free heart 39%) from ischemia/reperfusion injury in Langendorff hearts. In perfused fura-2 loaded mitochondria preparation, mitochondrial Ca^<2+> by acidification and Ca changes similar to reperfusion after global ischemia were suppressed with both NHE inhibitors. SM-197378 was found to directly quench the active oxygen radical, though SM-198110 had no eff … More ect. The number of apoptotic cells after long ischemia by reperfusion was significantly smaller in SM-197278-treated than SM-198110-treated hearts, consist with the level of activity of caspase-3 (Hotta et al., 2003).3.5-HT_<1A> or cyclic dipeptides (in beer or the distilled residue of millet brandy) had a beneficial effect against ischemia/reperfusion injury with Alp contents, quenching the active oxygen radical and inhibition of mitochondrial Ca^<2+> by acidification or Ca^<2+> contents of perfusate. These compounds also depressed apoptotic cell and the level of activity of caspase-3 (Huang and Akutagawa et al., 2004).4.Atractyroside (10^<->3 M), which opens mitochondrial permeability transition pores (MPTP) also caused similar increases in mitochondrial Ca^<2+> by acidification or Ca^<2+> content change. Cyclosporine A (10^<-4> M), which inhibits MPTP or many drugs that promote good recovery of the LVDP in the Langendorff ischemia/reperfusion injury model, were also suppressed, but not FK506 (10^<-4> M), which does not inhibit MPTP (Hotta et al., 2004). Less