Department of Cardiology, and Department of Neurology; Peking Union Medical College Hospital, Beijing, China.
Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):2054-2061. doi: 10.26355/eurrev_202002_20383.
The aim of this study was to explore the influence of hydrogen sulfide (H2S) on cardiomyocyte apoptosis in rats with myocardial ischemia-reperfusion injury via the c-Jun N-terminal kinase (JNK) pathway.
A total of 60 normal female Sprague-Dawley (SD) rats aged 38 weeks were divided into 3 groups, including the sham operation group (n=20), ischemia group (n=20) and ischemia + sodium hydrosulfide (NaHS) group (n=20). Subsequently, differences in cardiac function, the morphology of myocardial tissues, protein expression of JNK2, the content of plasma H2S and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), cystathionine-γ-lyase (CSE) and glutathione peroxidase (GSH-Px) were analyzed among rats in all groups.
Left ventricular diastolic pressure (LVDP) and maximum rate of pressure rise/fall (± dP/dtmax) were the highest in of rats of the sham operation group and the lowest in the ischemia group. Meanwhile, they were significantly elevated in the ischemia + NaHS group compared with those in the ischemia group (p<0.01). Left ventricular end-diastolic pressure (LVEDP) was the lowest in rats of the sham operation group and the highest in the ischemia group. Similarly, it decreased markedly in the ischemia + NaHS group compared with the ischemia group (p<0.01). Compared with the sham operation group, the perinuclear space in the myocardium was gradually larger, the arrangement of fibers became significantly more disordered, and the damage of mitochondrial cristae and membrane was remarkably more severe in rats in the ischemia group. Compared with the ischemia group, the above-mentioned conditions of rat cardiomyocytes were markedly improved (p<0.01). Meanwhile, the content of H2S and activity of CSE in the cardiomyocytes were altered in rats of the ischemia + NaHS group. Western blotting results indicated that, compared with the sham operation group, both the ischemia group and ischemia + NaHS group showed significantly up-regulated protein expression level of phosphorylated JNK2, with the highest level in the ischemia group. The content of MDA in rat myocardial tissues was markedly higher in the ischemia group than that of the ischemia + NaHS group, with the lowest level in the sham operation group (p<0.01). Additionally, the activity of SOD and GSH-Px in rat myocardial tissues was remarkably worse in the ischemia group than that of the ischemia + NaHS group, and it was the strongest in the sham operation group (p<0.01).
H2S inhibits the activity of the JNK pathway, decreases its phosphorylation level and down-regulates the protein expression level of JNK2, thereby protecting against myocardial ischemia-reperfusion injury.
本研究旨在探讨通过 c-Jun N 末端激酶（JNK）通路研究硫化氢（H2S）对心肌缺血再灌注损伤大鼠心肌细胞凋亡的影响。
将 60 只 38 周龄的正常雌性 Sprague-Dawley（SD）大鼠随机分为假手术组（n=20）、缺血组（n=20）和缺血+硫氢化钠（NaHS）组（n=20）。随后，分析各组大鼠心功能、心肌组织形态、JNK2 蛋白表达、血浆 H2S 和丙二醛（MDA）含量、超氧化物歧化酶（SOD）、胱硫醚-γ-裂解酶（CSE）和谷胱甘肽过氧化物酶（GSH-Px）活性的差异。
假手术组大鼠左心室舒张末期压（LVDP）和最大压力上升/下降率（± dP/dtmax）最高，缺血组最低，缺血+NaHS 组明显高于缺血组（p<0.01）。假手术组大鼠左心室舒张末期压（LVEDP）最低，缺血组最高，缺血+NaHS 组明显低于缺血组（p<0.01）。与假手术组相比，心肌细胞核周空间逐渐增大，纤维排列明显紊乱，线粒体嵴和膜损伤明显加重。与缺血组相比，大鼠心肌细胞的上述情况明显改善（p<0.01）。同时，缺血+NaHS 组大鼠心肌细胞中 H2S 含量和 CSE 活性发生改变。Western blot 结果表明，与假手术组相比，缺血组和缺血+NaHS 组磷酸化 JNK2 蛋白表达水平均显著上调，其中缺血组最高。缺血组大鼠心肌组织 MDA 含量明显高于缺血+NaHS 组，假手术组最低（p<0.01）。此外，缺血组大鼠心肌组织 SOD 和 GSH-Px 活性明显低于缺血+NaHS 组，假手术组最强（p<0.01）。
H2S 抑制 JNK 通路活性，降低其磷酸化水平，下调 JNK2 蛋白表达水平，从而起到心肌缺血再灌注损伤的保护作用。
