Welsh School of Pharmacy, Cardiff University, Cardiff, United Kingdom, Royal Veterinary College, University of London, London, United Kingdom.
J Cardiovasc Pharmacol Ther. 2010 Mar;15(1):53-9. doi: 10.1177/1074248409357743.
Hydrogen sulfide (H( 2)S) is a biological mediator produced by enzyme-regulated pathways from L-cysteine, which is a substrate for cystathionine-gamma-lyase (CSE). In myocardium, endogenously and exogenously administered H(2)S has been shown to protect against ischemia-reperfusion injury. We hypothesized that L-cysteine exerts its protective action through stimulation of H(2)S production. Rat isolated hearts were Langendorff-perfused and underwent 35-minute regional ischemia and 120-minute reperfusion. L-cysteine perfusion from 10 minutes before ischemia until 10 minutes after reperfusion limited infarct size in a concentration-dependent manner, maximal at 1 mmol/L (control 36.4% +/- 2.4% vs L-cysteine 24.3% +/- 3.4%, P < .05). This protective action was attenuated by the CSE inhibitor, DL-propargylglycine (PAG) 1 mmol/L (31.4 +/- 5.9%, not significant vs control) but administration of the CSE cofactor pyridoxal-5'-phosphate (PLP) 50 mumol/L did not enhance the effect of L-cysteine. Ten minutes normoxic perfusion with L-cysteine 1 mmol/L caused a 3-fold increase in myocardial H(2)S concentration (0.64 +/- 0.16 vs 2.01 +/- 0.07 mumol/g protein, P < .01), an effect that was significantly attenuated by PAG (1.17 +/- 0.15 mumol/g protein). These data provide evidence that exogenous L-cysteine administration limits ischemia-reperfusion injury through a mechanism that appears to be at least partially dependent on H(2)S synthesis.
硫化氢 (H₂S) 是一种生物调节剂，由 L-半胱氨酸通过酶调节途径产生，L-半胱氨酸是胱硫醚 γ-裂解酶 (CSE) 的底物。在内脏中，内源性和外源性给予 H₂S 已被证明可防止缺血再灌注损伤。我们假设 L-半胱氨酸通过刺激 H₂S 的产生来发挥其保护作用。大鼠离体心脏进行 Langendorff 灌注，并经历 35 分钟局部缺血和 120 分钟再灌注。从缺血前 10 分钟到再灌注后 10 分钟给予 L-半胱氨酸灌注以浓度依赖性方式限制梗死面积，最大浓度为 1 mmol/L（对照 36.4% +/- 2.4% 对 L-半胱氨酸 24.3% +/- 3.4%，P <.05）。这种保护作用被 CSE 抑制剂 DL-炔丙基甘氨酸 (PAG) 1 mmol/L 减弱（31.4 +/- 5.9%，与对照无显著差异），但给予 CSE 辅助因子吡哆醛-5'-磷酸酯 (PLP) 50 mumol/L 并未增强 L-半胱氨酸的作用。10 分钟正常氧灌注 1 mmol/L L-半胱氨酸使心肌 H₂S 浓度增加 3 倍（0.64 +/- 0.16 对 2.01 +/- 0.07 mumol/g 蛋白，P <.01），PAG 显著减弱该作用（1.17 +/- 0.15 mumol/g 蛋白）。这些数据提供证据表明，外源性 L-半胱氨酸给药通过一种机制限制缺血再灌注损伤，该机制似乎至少部分依赖于 H₂S 的合成。
