Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
Lab Invest. 2011 Jan;91(1):12-23. doi: 10.1038/labinvest.2010.156. Epub 2010 Aug 23.
Recently, sulfur dioxide (SO(2)) was discovered to be produced in the cardiovascular system and to influence important biological processes. Here, we investigated changes in endogenous SO(2)/glutamic oxaloacetic transaminase (GOT) pathway in the development of isoproterenol (ISO)-induced myocardial injury in rats and the regulatory effect of SO(2) on cardiac function, myocardial micro- and ultrastructure, and oxidative stress. Wistar male rats were divided into control, ISO-treated, ISO+SO(2), and SO(2) groups. At the termination of the experiment, parameters of cardiac function and hemodynamics were measured and the micro- and ultrastructure of myocardium and stereological ultrastructure of mitochondria were analyzed. Myocardial SO(2) content was detected by high-performance liquid chromatography. GOT (key enzyme for endogenous SO(2) production) activity and gene (GOT1 and GOT2) expressions were measured, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), hydrogen peroxide, and superoxide radical levels were assayed. SOD (SOD1 and SOD2) and GSH-Px (GSH-Px1) gene expressions were also detected. The results showed that SO(2) donor at a dose of 85 mg/(kg day) did not impact the cardiac function and structure of rats, but exerted a subtle influence on myocardial redox status. ISO-treated rats exhibited decreased cardiac function, damaged myocardial structures, and downregulated endogenous SO(2)/GOT pathway. Meanwhile, myocardial oxidative stress increased, whereas antioxidative capacity downregulated. Administration of SO(2) markedly improved cardiac function and ISO-induced myocardial damage by ameliorating the pathological structure of the myocardium and the mitochondria. At the same time, myocardial products of oxidative stress decreased, whereas antioxidative capacity increased. These results suggest that downregulation of the endogenous SO(2)/GOT pathway is likely involved in the pathogenesis of ISO-induced myocardial injury. SO(2) protects against ISO-induced myocardial injury associated with increased myocardial antioxidant capacity in rats.
最近，人们发现二氧化硫（SO(2)）在心血管系统中产生，并影响重要的生物学过程。在这里，我们研究了内源性 SO(2)/谷草转氨酶（GOT）途径在异丙肾上腺素（ISO）诱导的大鼠心肌损伤中的变化，以及 SO(2)对心脏功能、心肌微结构和超微结构以及氧化应激的调节作用。雄性 Wistar 大鼠分为对照组、ISO 处理组、ISO+SO(2)组和 SO(2)组。实验结束时，测量心脏功能和血液动力学参数，并分析心肌的微结构和超微结构以及线粒体的立体超微结构。通过高效液相色谱法检测心肌 SO(2)含量。测定 GOT（内源性 SO(2)产生的关键酶）活性和基因（GOT1 和 GOT2）表达，并测定超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢和超氧自由基水平。还检测了 SOD（SOD1 和 SOD2）和 GSH-Px（GSH-Px1）基因表达。结果表明，剂量为 85mg/（kg·天）的 SO(2)供体不会影响大鼠的心脏功能和结构，但对心肌氧化还原状态有微妙影响。ISO 处理的大鼠表现出心脏功能下降、心肌结构受损和内源性 SO(2)/GOT 途径下调。同时，心肌氧化应激增加，而抗氧化能力下降。SO(2)的给药显著改善了心脏功能和 ISO 诱导的心肌损伤，改善了心肌和线粒体的病理结构。同时，心肌氧化应激产物减少，而抗氧化能力增加。这些结果表明，内源性 SO(2)/GOT 途径的下调可能参与了 ISO 诱导的心肌损伤的发病机制。SO(2)通过增加心肌抗氧化能力来保护大鼠免受 ISO 诱导的心肌损伤。
