Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats
Endogenous sulfur dioxide protects against isoproterenol-induced myocardial injury and increases myocardial antioxidant capacity in rats
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DOI：
10.1038/labinvest.2010.156
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发表时间：
2011-01-01
影响因子：
5
通讯作者：
Du, Junbao
中科院分区：
文献类型：
--
作者：
Liang, Yinfang;Liu, Die;Du, Junbao
最近，二氧化硫（SO2）被发现在心血管系统中产生，并影响重要的生物过程。本研究探讨了异丙肾上腺素（ISO）诱导的大鼠心肌损伤过程中内源性SO2/谷草转氨酶（GOT）途径的变化，以及SO2对心功能、心肌微观和超微结构以及氧化应激的调节作用。Wistar雄性大鼠分为对照组、ISO组、ISO+SO2组和SO2组。实验结束时，测定心功能和血流动力学参数，并对心肌组织进行显微、超微结构和线粒体体视学超微结构分析。采用高效液相色谱法测定心肌SO2含量。测定GOT（内源SO2产生关键酶）活性和GOT 1、GOT 2基因表达，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。检测SOD（SOD 1和SOD 2）和GSH-Px（GSH-Px 1）基因表达。结果表明，SO_2供体85 mg/（kg·d）对大鼠心脏功能和结构无明显影响，但对心肌氧化还原状态有轻微影响。ISO处理的大鼠表现出心功能下降，心肌结构受损，内源性SO2/GOT通路下调。同时，心肌氧化应激增强，抗氧化能力下降。SO 2通过改善心肌和线粒体的病理结构，显著改善心功能和ISO引起的心肌损伤。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SO2/GOT通路的下调可能参与了ISO诱导的心肌损伤的发病机制。SO2对ISO诱导的大鼠心肌损伤的保护作用与心肌抗氧化能力的增加有关。实验室调查（2011）91，12-23; doi：10.1038/labinvest.2010.156;在线发表2010年8月23日
Recently, sulfur dioxide (SO2) was discovered to be produced in the cardiovascular system and to influence important biological processes. Here, we investigated changes in endogenous SO2/glutamic oxaloacetic transaminase (GOT) pathway in the development of isoproterenol (ISO)-induced myocardial injury in rats and the regulatory effect of SO2 on cardiac function, myocardial micro-and ultrastructure, and oxidative stress. Wistar male rats were divided into control, ISO-treated, ISO+SO2, and SO2 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 SO2 content was detected by high-performance liquid chromatography. GOT (key enzyme for endogenous SO2 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 SO2 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 SO2/GOT pathway. Meanwhile, myocardial oxidative stress increased, whereas antioxidative capacity downregulated. Administration of SO2 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 SO2/GOT pathway is likely involved in the pathogenesis of ISO-induced myocardial injury. SO2 protects against ISO-induced myocardial injury associated with increased myocardial antioxidant capacity in rats. Laboratory Investigation (2011) 91, 12-23; doi:10.1038/labinvest.2010.156; published online 23 August 2010