Zhu Yi Zhun, Wang Zhong Jing, Ho Peiying, Loke Yoke Yun, Zhu Yi Chun, Huang Shan Hong, Tan Chee Sin, Whiteman Matt, Lu Jia, Moore Philip K
Department of Pharmacology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 117597.
J Appl Physiol (1985). 2007 Jan;102(1):261-8. doi: 10.1152/japplphysiol.00096.2006. Epub 2006 Oct 12.
The role of hydrogen sulfide (H(2)S) in myocardial infarction (MI) has not been previously studied. We therefore investigated the effect of H(2)S in a rat model of MI in vivo. Animals were randomly divided into three groups (n = 80) and received either vehicle, 14 micromol/kg of sodium hydrosulfide (NaHS), or 50 mg/kg propargylglycine (PAG) everyday for 1 wk before surgery, and the treatment was continued for a further 2 days after MI when the animals were killed. The mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS-treated (P < 0.05 vs. vehicle) groups. Infarct size was 52.9 +/- 3.5% in vehicle-treated, 62.9 +/- 7.6% in PAG-treated, and 43.4 +/- 2.8% in NaHS-treated (P < 0.05 vs. vehicle) groups. Plasma H(2)S concentration was significantly increased after MI (59.2 +/- 7.16 microM) compared with the baseline concentration (i.e., 38.2 +/- 2.07 microM before MI; P < 0.05). Elevated plasma H(2)S after MI was abolished by treatment of animals with PAG (39.2 +/- 5.02 microM). We further showed for the first time cystathionine-gamma-lyase protein localization in the myocardium of the infarct area by using immunohistochemical staining. In the hypoxic vascular smooth muscle cells, we found that cell death was increased under the stimuli of hypoxia but that the increased cell death was attenuated by the pretreatment of NaHS (71 +/- 1.2% cell viability in hypoxic vehicle vs. 95 +/- 2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H(2)S was cardioprotective in the rat model of MI. PAG reduced endogenous H(2)S production after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H(2)S might provide a novel approach to the treatment of MI.
硫化氢（H₂S）在心肌梗死（MI）中的作用此前尚未得到研究。因此，我们在体内的大鼠心肌梗死模型中研究了H₂S的作用。动物被随机分为三组（n = 80），在手术前每天分别给予溶剂、14微摩尔/千克的氢硫化钠（NaHS）或50毫克/千克的炔丙基甘氨酸（PAG），持续1周，并且在心肌梗死后动物被处死时，治疗再持续2天。溶剂处理组的死亡率为35%，PAG处理组为40%，NaHS处理组为27.5%（与溶剂处理组相比，P < 0.05）。梗死面积在溶剂处理组为52.9±3.5%，PAG处理组为62.9±7.6%，NaHS处理组为43.4±2.8%（与溶剂处理组相比，P < 0.05）。与基线浓度（即心肌梗死前38.2±2.07微摩尔）相比，心肌梗死后血浆H₂S浓度显著升高（59.2±7.16微摩尔；P < 0.05）。用PAG处理动物后，心肌梗死后升高的血浆H₂S被消除（39.2±5.02微摩尔）。我们首次通过免疫组织化学染色显示了胱硫醚-γ-裂解酶蛋白在梗死区域心肌中的定位。在缺氧的血管平滑肌细胞中，我们发现缺氧刺激下细胞死亡增加，但NaHS预处理可减轻增加的细胞死亡（缺氧溶剂处理组细胞活力为71±1.2%，非缺氧对照组为95±2.3%；P < 0.05）。总之，内源性H₂S在大鼠心肌梗死模型中具有心脏保护作用。PAG通过抑制胱硫醚-γ-裂解酶降低心肌梗死后内源性H₂S的产生。结果表明，H₂S可能为心肌梗死的治疗提供一种新方法。
