Vascular Biology Lab, SASTRA University, Thanjavur, Tamilnadu, 613401, India.
Vascular Biology Lab, SASTRA University, Thanjavur, Tamilnadu, 613401, India.
Biomed Pharmacother. 2018 Jan;97:271-279. doi: 10.1016/j.biopha.2017.10.118. Epub 2017 Nov 6.
Cardio-protective effect of hydrogen sulfide (HS) against myocardial ischemia reperfusion injury (I/R) via preservation of mitochondria is well documented. But the distinct role of exogenous and endogenous HS in cardio-protection and its dependency on functional cardiac mitochondria is not understood. The present study was designed to investigate the role of exogenous HS preconditioning on cardiac mitochondrial subpopulation namely interfibrillar (IFM) and subsarcolemmal (SSM), in attenuating I/R injury in an isolated rat heart model in the absence of endogenous HS production. The well-known inhibitor of endogenous HS production DL-propargylglycine (cystathionine gamma lyase inhibitor) used for this purpose. Our previous studies revealed that NaSH (a HS donor) preconditioning at a dose of 20μM significantly reduced the infarct size and preserved the functional activities of IFM. However, this protective effect significantly declined, when the heart preconditioned with NaSH in the presence of PAG. Apparently, cardiac recovery was improved hemodynamically to a minimal level by increased concentration of NaSH (40μM). The rat heart perfused with 2, 4 dinitrophenol a mitochondrial uncoupler, before NaSH preconditioning to understand the mitochondrial dependency of exogenous NaSH, we found that cardio-protective effect of NaSH was negated even with higher concentration of HS. The result indicates that exogenous NaSH mediated cardio protection depends on functional cardiac mitochondria. However, no functional difference between the subpopulation i.e., interfibrillar and subsarcolemmal mitochondria observed with NaSH preconditioning in the presence of PAG.
硫化氢 (HS) 通过保护线粒体对心肌缺血再灌注损伤 (I/R) 具有心脏保护作用，这已得到充分证实。但是，外源性和内源性 HS 在心脏保护中的作用及其对功能性心肌线粒体的依赖性尚不清楚。本研究旨在研究外源性 HS 预处理对心肌线粒体亚群（即纤维间 (IFM) 和肌小节下 (SSM)）的作用，以在缺乏内源性 HS 产生的情况下减轻离体大鼠心脏模型中的 I/R 损伤。为此目的使用了内源性 HS 产生的众所周知抑制剂 DL-丙炔甘氨酸 (胱硫醚 γ 裂解酶抑制剂)。我们之前的研究表明，20μM 的 NaSH（HS 供体）预处理可显著减少梗死面积并保持 IFM 的功能活性。然而，当心脏在 PAG 存在下用 NaSH 预处理时，这种保护作用显著下降。显然，通过增加 NaSH 的浓度（40μM），心脏的血流动力学恢复得到了改善，达到了最低水平。在用线粒体解偶联剂 2,4-二硝基苯酚灌注大鼠心脏之前，进行 NaSH 预处理以了解外源性 NaSH 的线粒体依赖性，我们发现即使使用更高浓度的 HS，NaSH 的心脏保护作用也被否定。结果表明，外源性 NaSH 介导的心脏保护依赖于功能性心肌线粒体。然而，在用 PAG 预处理时，在 NaSH 预处理下观察到亚群之间（即纤维间和肌小节下）没有功能差异。
