ROS-Dependent Neuroprotective Effects of NaHS in Ischemia Brain Injury Involves the PARP/AIF Pathway

Background/Aims: Stroke is among the top causes of death worldwide. Neuroprotective agents are thus considered as potentially powerful treatment of stroke. Methods: Using both HT22 cells and male Sprague-Dawley rats as in vitro and in vivo models, we investigated the effect of NaHS, an exogenous donor of H2S, on the focal cerebral ischemia-reperfusion (I/R) induced brain injury. Results: Administration of NaHS significantly decreased the brain infarcted area as compared to the I/R group in a dose-dependent manner. Mechanistic studies demonstrated that NaHS-treated rats displayed significant reduction of malondialdehyde content, and strikingly increased activity of superoxide dismutases and glutathione peroxidase in the brain tissues compared with I/R group. The enhanced antioxidant capacity as well as restored mitochondrial function are NaHS-treatment correlated with decreased cellular reactive oxygen species level and compromised apoptosis in vitro or in vivo in the presence of NaHS compared with control. Further analysis revealed that the inhibition of PARP-1 cleavage and AIF translocation are involved in the neuroprotective effects of NaHS. Conclusion: Collectively, our results suggest that NaHS has potent protective effects against the brain injury induced by I/R. NaHS is possibly effective through inhibition of oxidative stress and apoptosis. Copyright (C) 2015 S. Karger AG, Basel

背景/目的：中风是全球主要的死亡原因之一。因此，神经保护剂被认为是治疗中风的潜在有力手段。 方法：我们使用HT22细胞和雄性Sprague - Dawley大鼠作为体外和体内模型，研究了硫化氢（H₂S）的外源性供体硫氢化钠（NaHS）对局部脑缺血再灌注（I/R）诱导的脑损伤的影响。 结果：与I/R组相比，给予NaHS以剂量依赖的方式显著减少了脑梗死面积。机制研究表明，与I/R组相比，NaHS处理的大鼠脑组织中丙二醛含量显著降低，超氧化物歧化酶和谷胱甘肽过氧化物酶活性显著提高。与对照组相比，在NaHS存在的情况下，无论是体外还是体内，抗氧化能力的增强以及线粒体功能的恢复都与细胞活性氧水平的降低和细胞凋亡的减少相关。进一步分析显示，PARP - 1裂解的抑制和AIF易位参与了NaHS的神经保护作用。 结论：总体而言，我们的研究结果表明NaHS对I/R诱导的脑损伤具有有效的保护作用。NaHS可能通过抑制氧化应激和细胞凋亡发挥作用。 版权所有（C）2015 S. Karger AG，巴塞尔