Hydrogen Sulfide Protects the Brain Against Ischemic Reperfusion Injury in a Transient Model of Focal Cerebral Ischemia
Hydrogen Sulfide Protects the Brain Against Ischemic Reperfusion Injury in a Transient Model of Focal Cerebral Ischemia
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DOI：
10.1007/s12031-014-0284-9
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发表时间：
2014-10-01
影响因子：
3.1
通讯作者：
Gheibi, Azam
中科院分区：
文献类型：
--
作者：
Gheibi, Sevda;Aboutaleb, Nahid;Gheibi, Azam
硫化氢（H2S）是一种常见的有毒气体，被认为是一种内源性神经调质，在中枢神经系统的生理和病理状态下发挥着多种作用，尤其是在继发性神经元损伤中。最近的研究表明，相对高浓度的硫化氢（H2S）在大脑中，内源性和外源性H2S在体外和体内缺血性损伤模型的细胞保护作用。H2S通过作为抗氧化剂、抗炎和抗凋亡介质以及通过改善神经功能来保护神经元。此外，它保护神经元免受谷氨酸毒性。因此，本研究的目的是确定H2S是否在短暂的局灶性脑缺血中提供保护。局灶性缺血60分钟大脑中动脉闭塞（MCAO），然后再灌注23小时。在缺血开始时腹膜内注射（IP）生理盐水作为溶媒和NaHS（H2S供体; 1和5 mg）。在MCAO后24小时评估脑梗死体积、脑水肿和细胞凋亡，NaHS 1和5 mg剂量治疗显著减少总梗死体积分别为29和51%（P < 0.001）。此外，NaHS在1和5毫克的剂量减少脑水肿TUNEL阳性细胞数减少，细胞凋亡减少（P < 0.05）（P < 0.001）。本研究表明，H2S治疗可能通过阻断程序性细胞死亡以剂量依赖的方式减轻脑损伤和缺血后脑水肿。我们认为H2S可能是一个有希望的治疗中风的靶点。尽管需要更多的研究来考虑H2S在中风患者中的潜在治疗效果。
Hydrogen sulfide (H2S), a well-known toxic gas, is regarded as endogenous neuromodulator and plays multiple roles in the central nervous system under physiological and pathological states, especially in secondary neuronal injury. Recent studies have shown relatively high concentrations of hydrogen sulfide (H2S) in the brain and also cytoprotective effects of endogenous and exogenous H2S in models of in vitro and in vivo ischemic injury. H2S protects neurons by functioning as an anti-oxidant, anti-inflammatory, and anti-apoptotic mediator and by improving neurological function. Moreover, it protects neurons from glutamate toxicity. Therefore, the present study aimed to determine whether H2S provides protection in transient focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and NaHS (H2S donor; 1 and 5 mg) were intraperitoneally injected (IP) at the beginning of ischemia. Infarct volume, brain edema, and apoptosis were assessed 24 h after MCAO.Treatment with NaHS at doses of 1 and 5 mg markedly reduced total infarct volumes by 29 and 51 %, respectively (P < 0.001). In addition, NaHS at doses of 1 and 5 mg reduced brain edema (P < 0.05) and inhibited apoptosis by decreasing positive TUNEL cells (P < 0.001).The present study shows that treatment with H2S reduces brain injuries and postischemic cerebral edema in a dose-dependent manner likely through the blocking programmed cell death.We propose that H2S might be a promising therapeutic target for stroke, although more researches are necessary to take into account the potential therapeutic effects of H2S in stroke patients.