Cancer Research Center, Tehran University of Medical Science, Tehran, Iran.
Peptides. 2012 Jul;36(1):71-7. doi: 10.1016/j.peptides.2012.03.023. Epub 2012 Apr 5.
The current study examines the protective effect of oxytocin (OT) on cardiomyocyte apoptosis modulated by mitochondrial ATP-dependent potassium (mitoKATP) channel and permeability transition pore (mPTP) in the preconditioned myocardium of anesthetized rats. Eighty rats were equally divided into eight groups. The hearts of all animals except for the sham group were subjected to 25 min ischemia and 120 min reperfusion. Oxytocin, 5-hydroxydeconoate (5-HD), a specific inhibitor of the mitoKATP channel, and atractyloside (ATRC), an mPTP opener, were used prior to ischemia. Hemodynamic parameters were recorded throughout the experiment. Evaluations were made by infarct size, plasma lactate dehydrogenase level (LDH), transmission electron microscopy (TEM) and immunohistochemistry studies. OT prevented mean arterial pressure drop during early phase of ischemia and reperfusion. Treatment with OT before IR induction normalizes cardiomyocytes both in light microscopy and TEM observations. In addition, OT significantly reduced TUNEL- and increased Bcl-2-labeled positive cell number relative to IR (p<0.05). However, 5HD or ATRC inhibited the protective effects of OT on cardiomyocytes damaged by IR (p<0.05). Ultrastructural changes including extensive myofibril loss, sarcolemmal disruption and mitochondrial swelling due to amorphous dens bodies indicate necrosis induction in 5HD and ATRC as well as in IR groups. Restoration of immunohistochemistry parameters and protection against IR-induced ultrastructural changes confirm OT cardioprotective effects via mitoKATP channel and mPTP modulation in apoptosis induced by ischemia-reperfusion.
本研究探讨了催产素（OT）对麻醉大鼠预处理心肌中线粒体 ATP 依赖性钾（mitoKATP）通道和通透性转换孔（mPTP）调节的心肌细胞凋亡的保护作用。80 只大鼠等分为 8 组。除假手术组外，所有动物的心脏均经历 25 分钟缺血和 120 分钟再灌注。在缺血前使用催产素、5-羟基癸酸（5-HD），一种 mitoKATP 通道的特异性抑制剂，以及阿托西班（ATRC），一种 mPTP 开放剂。整个实验过程中记录血流动力学参数。通过梗死面积、血浆乳酸脱氢酶水平（LDH）、透射电镜（TEM）和免疫组织化学研究进行评估。OT 可防止缺血早期和再灌注期间平均动脉压下降。IR 诱导前用 OT 处理可使光镜和 TEM 观察到的心肌细胞正常化。此外，OT 可显著减少 TUNEL 并增加 Bcl-2 标记的阳性细胞数相对于 IR（p<0.05）。然而，5-HD 或 ATRC 抑制了 OT 对 IR 损伤的心肌细胞的保护作用（p<0.05）。超微结构变化包括广泛的肌原纤维丢失、细胞膜破裂和由于无定形致密体导致的线粒体肿胀，表明 5-HD 和 ATRC 以及 IR 组诱导坏死。免疫组织化学参数的恢复和对 IR 诱导的超微结构变化的保护作用证实了 OT 通过 mitoKATP 通道和 mPTP 调节在缺血再灌注诱导的凋亡中具有心脏保护作用。
