Int J Cardiol 2011 Oct;152 (2): 177-83. [IF:6.802]
The protective role of hydrogen sulfide in myocardial ischemia-reperfusion-induced injury in diabetic rats.
Gao Y , Yao X , Zhang Y , Li W , Kang K , Sun L , Sun X .
Department of ICU, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
中国哈尔滨医科大学附属第四医院重症监护病房
Abstract
Hydrogen sulfide (H(2)S) displays anti-inflammatory and cytoprotective activities to attenuate myocardial ischemia-reperfusion (MIR)-induced injury, but its role in MIR in diabetics is not known. This study was undertaken to investigate whether H(2)S plays a protective role in MIR in diabetic rats. Diabetes was induced by streptozocin in Wistar rats, which were subjected to myocardial ischemia by blocking the left circumflex artery for 30 min, followed by 2h reperfusion. dl-propargylglycine (PAG) and sodium hydrosulfide (NaHS) were administered to the rats to investigate their effects on severity of MIR-induced injury. Diabetic rats had smaller myocardial infarct sizes and higher serum levels of H(2)S (both P < 0.05) than non-diabetics when they underwent MIR. MIR significantly increased the serum level of H(2)S (49.5 ± 7.1 μM), H(2)S-synthesizing activity (7.4 ± 1.6 nmol/mg) and the myocardial infarct size (44.0 ± 7.2%), compared with sham-operated diabetic rats (21.7 ± 2.1 μM, 0.15 ± 0.4 nmol/mg and 1.2 ± 0.4%, respectively). Administration of NaHS increased the H(2)S level (65.8 ± 6.9 μM) and had little effect on H(2)S production activity (6.5 ± 2.2 nmol/mg), while PAG reduced both the H(2)S level (29.2 ± 5.0 μM) and H(2)S-synthesizing activity (2.2 ± 1.8 nmol/mg). NaHS significantly reduced the myocardial infarct size (31.2 ± 4.7%), inhibited the production of lipid peroxidation, MPO activity, and cell apoptosis, and downregulated expression of caspase-3, Fas, FasL, and TNF-α, which had been elevated by MIR, while PAG further increased the myocardial infarct size (58.3 ± 5.9%), and displayed opposite effects. The study indicates that H(2)S may play a protective role in MIR-induced myocardial injury in diabetics by its anti-apoptotic, anti-oxidative and anti-inflammatory activities.
摘要：
硫化氢(H(2)S)具有抗炎、细胞保护作用来减弱心肌缺血再灌注损伤，但它的作用在糖尿病患者中不为人所知。本研究旨在调查硫化氢是否对糖尿病小鼠心肌缺血再灌注有保护作用。使用链脲菌素（streptozocin）在Wistar鼠诱导糖尿病模型，通过阻断冠状动脉左旋支30分钟使其心肌缺血，然后再灌注2小时。研究消旋炔丙基甘氨酸和硫氢化钠对大鼠严重缺血再灌注损伤的作用。相对于非糖尿病鼠，在遭受缺血再灌注时糖尿病鼠有更小的心肌梗死面积和更高的血清硫化氢水平（二者P值均小于0.05）。与假手术糖尿病鼠组相比，缺血再灌注组的血清硫化氢水平(49.5 ± 7.1 μM)，硫化氢综合活性(7.4 ± 1.6 nmol/mg)和心肌梗死面积(44.0 ± 7.2%)显著增加（假手术组分别为21.7 ± 2.1 μM， 0.15 ± 0.4 nmol/mg，1.2 ± 0.4%）。给予NaHS能增加硫化氢水平(65.8 ± 6.9 μM)，几乎不影响硫化氢产生活性(6.5 ± 2.2 nmol/mg)，而PAG则降低硫化氢水平(29.2 ± 5.0 μM)及其综合活性(2.2 ± 1.8 nmol/mg)。NaHS能显著减少心肌梗死面积(31.2 ± 4.7%)，抑制脂质过氧化作用、MPO活性及细胞凋亡，并能下调引起缺血再灌注的细胞凋亡蛋白酶、Fas、FasL和肿瘤坏死因子，而PAG则促进心肌梗死面积增加(58.3 ± 5.9%)，具有反作用。该研究表面硫化氢可能在糖尿病患者的缺血再灌注损伤中具有保护性作用，其机制为硫化氢的抗细胞凋亡、抗氧化和抗炎作用。
