Gaseous hydrogen sulfide protects against myocardial ischemia-reperfusion injury in mice partially independent from hypometabolism.
Gaseous hydrogen sulfide protects against myocardial ischemia-reperfusion injury in mice partially independent from hypometabolism.
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气态硫化物可预防部分独立于低代谢的小鼠的心肌缺血 - 再灌注损伤。
DOI：
10.1371/journal.pone.0063291
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
van Goor H
中科院分区：
文献类型：
--
作者：
Snijder PM;de Boer RA;Bos EM;van den Born JC;Ruifrok WP;Vreeswijk-Baudoin I;van Dijk MC;Hillebrands JL;Leuvenink HG;van Goor H
缺血-再灌注损伤（IRI）是多种病理过程导致心脏损伤的主要原因。气态硫化氢（H2S）在IRI期间通过诱导小鼠的低代谢状态而具有保护作用，这与抗凋亡、抗炎和抗氧化特性有关。我们研究了气态H2S给药是否对心脏IRI具有保护作用，以及非低代谢浓度的H2S是否具有类似的保护作用。雄性C57 BL/6小鼠在缺血前30分钟开始接受0、10或100 ppm H2S-N2混合物，直至再灌注前5分钟。通过暂时结扎左冠状动脉30分钟造成IRI。使用高分辨率呼吸测量设备评估CO2产生，并使用内部变送器测量血压。通过组织学和分子分析评估H2S的影响。用100 ppm H2S处理使CO2产生减少72%，血压降低14%，心率降低25%，而用10 ppm H2S处理则没有影响。在再灌注第1天，10 ppm H2S对坏死没有影响，而用100 ppm H2S处理使坏死减少62%（p<0.05）。再灌注后7天，与IRI动物相比，10 ppm（p<0.01）和100 ppm（p<0.05）H2S均显示纤维化减少。10 ppm和100 ppm H2S分别使粒细胞内流减少43%（p<0.05）和60%（p<0.001）。在再灌注后7天，10和100 ppm H2S分别使纤维连接蛋白的表达降低63%（p<0.05）和67%（p<0.01），ANP分别降低84%和63%（p<0.05）。当在心脏缺血性损伤期间给药时，H2S的气体给药具有保护作用。虽然低代谢仅限于小动物，但我们现在表明，低浓度的非低代谢的H2S在IRI中也具有保护作用。由于IRI是经皮冠状动脉介入治疗和心脏移植过程中心肌损伤的常见原因，H2S治疗可能会导致新的治疗方式。
Ischemia-reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes. Gaseous hydrogen sulfide (H2S) is protective during IRI by inducing a hypometabolic state in mice which is associated with anti-apoptotic, anti-inflammatory and antioxidant properties. We investigated whether gaseous H2S administration is protective in cardiac IRI and whether non-hypometabolic concentrations of H2S have similar protective properties. Male C57BL/6 mice received a 0, 10, or 100 ppm H2S-N2 mixture starting 30 minutes prior to ischemia until 5 minutes pre-reperfusion. IRI was inflicted by temporary ligation of the left coronary artery for 30 minutes. High-resolution respirometry equipment was used to assess CO2-production and blood pressure was measured using internal transmitters. The effects of H2S were assessed by histological and molecular analysis. Treatment with 100 ppm H2S decreased CO2-production by 72%, blood pressure by 14% and heart rate by 25%, while treatment with 10 ppm H2S had no effects. At day 1 of reperfusion 10 ppm H2S showed no effect on necrosis, while treatment with 100 ppm H2S reduced necrosis by 62% (p<0.05). Seven days post-reperfusion, both 10 ppm (p<0.01) and 100 ppm (p<0.05) H2S showed a reduction in fibrosis compared to IRI animals. Both 10 ppm and 100 ppm H2S reduced granulocyte-influx by 43% (p<0.05) and 60% (p<0.001), respectively. At 7 days post-reperfusion both 10 and 100 ppm H2S reduced expression of fibronectin by 63% (p<0.05) and 67% (p<0.01) and ANP by 84% and 63% (p<0.05), respectively. Gaseous administration of H2S is protective when administered during a cardiac ischemic insult. Although hypometabolism is restricted to small animals, we now showed that low non-hypometabolic concentrations of H2S also have protective properties in IRI. Since IRI is a frequent cause of myocardial damage during percutaneous coronary intervention and cardiac transplantation, H2S treatment might lead to novel therapeutical modalities.
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影响因子：
37.8
作者：
Calvert JW;Elston M;Nicholson CK;Gundewar S;Jha S;Elrod JW;Ramachandran A;Lefer DJ
通讯作者：
Lefer DJ
影响因子：
3.7
作者：
De Silva TM;Brait VH;Drummond GR;Sobey CG;Miller AA
通讯作者：
Miller AA
影响因子：
10.8
作者：
Hishikari, Keiichi;Suzuki, Jun-ichi;Isobe, Mitsuaki
通讯作者：
Isobe, Mitsuaki
影响因子：
4.7
作者：
Hu, Li-Fang;Wong, Peter T. -H.;Bian, Jin-Song
通讯作者：
Bian, Jin-Song
影响因子：
56.9
作者：
Blackstone, E;Morrison, M;Roth, MB
通讯作者：
Roth, MB