Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes
Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes
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DOI：
10.1016/j.yjmcc.2005.10.003
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发表时间：
2006-01-01
影响因子：
5
通讯作者：
Bian, JS
中科院分区：
文献类型：
--
作者：
Pan, TT;Feng, ZN;Bian, JS
在含有糖酵解抑制剂2-脱氧-D-葡萄糖（2-DOG）的无葡萄糖缓冲液中，研究了硫化氢（H2S）对严重代谢抑制（MI）的离体大鼠心室肌细胞的保护作用。用10（-5）~ 10（-4）mol/L的NaHS（H_2S供体）预处理30 min，细胞活力和杆状细胞比例随NaHS浓度的增加而增加。时程研究表明，NaHS诱导的心脏保护作用发生在2个时间窗（类似于1 h和16-28 h）。为了观察内源性H2S是否可能参与IP的延迟心脏保护反应，使用DL-炔丙基甘氨酸（PAG）和β-氰基-L-丙氨酸（BCA;两种H2S生物合成抑制剂）。两种药物均显著减弱MI产生的心脏保护作用，使用细胞活力、细胞损伤指数和电诱导的[Ca 2 +]（i）瞬变作为终点。提示内源性H2S在心肌缺血预处理的心肌保护中起重要作用。为了确定H2S心脏保护作用的机制，我们检查了格列本脲（一种非选择性K-ATP通道阻滞剂）、5-羟基癸酸（5-HD，一种线粒体K-ATP阻滞剂）和HMR-1098（一种肌膜K-ATP阻滞剂）阻断K-ATP通道的作用。NaHS的心脏保护作用被格列本脲和HMR-1098处理显著减弱，但不被5-HD处理）。用L-NG硝基精氨酸甲酯（L-NAME）抑制NO的产生也减弱了NaHS的心脏保护作用。总之，我们的研究结果提供了第一个证据表明，H2S可能保护心脏最可能通过激活肌膜K-ATP通道和/或挑起NO释放和代谢性缺血预处理的心脏保护作用，至少部分是由内源性H2S介导的。(c)2005爱思唯尔有限公司保留所有权利。
The possible role of hydrogen Sulfide (H2S) in cardioprotection was investigated in isolated rat ventricular myocytes exposed to severe metabolic inhibition (MI) in glucose-free buffer containing 2-deoxy-D-glucose (2-DOG), an inhibitor of glycolysis. Pretreatment (30 min) with NaHS (a H2S donor) at concentrations of 10(-5) to 10(-4) mol/L caused a concentration related increase in cell viability and the ratio of rod-shaped cells. A time course study showed that NaHS-induced cardioprotection occurred in 2 time windows (similar to 1 h and 16-28 h). To observe whether endogenous H2S may be involved in the delayed cardioprotection response of IP, DL-propargylglycine (PAG) and beta-cyano-L-alanine (BCA; two inhibitors of H2S biosynthesis) were Used. Both drugs significantly attenuated the cardioprotection produced by MI Using cell viability, cellular injury index, and electrically-induced [Ca2+](i) transients as end-points. These data suggest that endogenous H2S plays an important role in the cardioprotection following MI preconditioning. In an attempt to determine the mechanism of the cardioprotective effect of H2S, we examined the effect of blocking K-ATP channels with glibenclamide (a non-selective K-ATP channel blocker), 5-hydroxydecanoic acid (5-HD, a mitochondrial K-ATP blocker), and HMR-1098 (a sarcoleminal K-ATP blocker). The cardioprotective effects of NaHS were significantly attenuated by glibenclamide and HMR-1098 treatment but not by 5-HD). Inhibition of NO production with L-NG nitroarginine methyl ester (L-NAME) also attenuated the cardioprotection of NaHS. In conclusion, our findings provide the first evidence that H2S may protect the heart most probably by activating sarcolemmal K-ATP channels and/or provoking NO release and the cardioprotective effects of metabolic ischemic preconditioning is, at least partially, mediated by endogenous H2S. (c) 2005 Elsevier Ltd. All rights reserved.