Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Lab of Laboratory Animal Science, Department of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China.
Nitric Oxide. 2017 Jul 1;67:10-25. doi: 10.1016/j.niox.2017.04.010. Epub 2017 Apr 24.
Takotsubo cardiomyopathy (TCM) is characterized by transient left ventricular apical ballooning with the absence of coronary occlusion, which is an acute cardiac syndrome with substantial morbidity and mortality. It was reported that reduced endogenous hydrogen sulfide (HS) levels may be related to various heart diseases. The present study investigated the mechanism by which HS administration modulates and protects cardiac function in TCM rats. In order to establish a TCM model, Sprague Dawley (SD) rats were injected with a single dose of β-adrenergic agonist isoprenaline (ISO). We found that ISO induced cardiac dysfunction, which was characterized by a significant decrease in left ventricular systolic pressure (LVSP), maximum contraction velocity (+dp/dtmax), maximum relaxation velocity (-dp/dtmax) and increased left ventricular end-diastolic pressure (LVEDP). Accordingly, we found that plasma and heart tissue HS levels in TCM rats decreased significantly, and cardiac cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) expression were lower. Moreover, cardiac dysfunction in TCM was associated with oxidative stress response and reactive oxygen species (ROS) formation. NADPH Oxidase 4 (NOX) and p67 protein expressions significantly increased in TCM cardiac tissues. In addition, Sodium hydrosulfide (NaHS) ameliorated ISO-induced cardiac dysfunction and reversed ISO-induced oxidative stress. This study revealed that HS exerted cardioprotective effects by reducing NADPH oxidase, which reduced ROS formation and prevented oxidative stress. Our study provided novel evidence that HS is protective in myocardial dysfunction in TCM rats and could be a therapeutic target for alleviating β-adrenergic system overstimulation-induced cardiovascular dysfunction.
心肌顿抑综合征（TCM）的特征是短暂的左心室心尖球囊样变，而不存在冠状动脉阻塞，这是一种具有高发病率和死亡率的急性心脏综合征。有报道称，内源性硫化氢（HS）水平降低可能与各种心脏病有关。本研究探讨了 HS 给药调节和保护 TCM 大鼠心脏功能的机制。为了建立 TCM 模型，向 Sprague Dawley（SD）大鼠单次注射β-肾上腺素能激动剂异丙肾上腺素（ISO）。我们发现 ISO 诱导的心脏功能障碍，其特征是左心室收缩压（LVSP）、最大收缩速度（+dp/dtmax）、最大松弛速度（-dp/dtmax）显著降低，左心室舒张末期压（LVEDP）升高。相应地，我们发现 TCM 大鼠的血浆和心脏组织 HS 水平显著降低，心脏胱硫醚γ-裂解酶（CSE）和 3-巯基丙酮酸硫转移酶（3-MST）表达降低。此外，TCM 中的心脏功能障碍与氧化应激反应和活性氧（ROS）形成有关。TCM 心脏组织中 NADPH 氧化酶 4（NOX）和 p67 蛋白表达显著增加。此外，硫氢化钠（NaHS）改善了 ISO 诱导的心脏功能障碍并逆转了 ISO 诱导的氧化应激。本研究表明，HS 通过减少 NADPH 氧化酶来发挥心脏保护作用，从而减少 ROS 形成并防止氧化应激。我们的研究提供了新的证据，表明 HS 在 TCM 大鼠心肌功能障碍中具有保护作用，可能是缓解β-肾上腺素能系统过度刺激引起的心血管功能障碍的治疗靶点。
