Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats
Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats
复制标题
硫化氢可改善大鼠蛛网膜下腔出血后的早期脑损伤
DOI：
10.1007/s12035-015-9304-1
复制
发表时间：
2016-08-01
影响因子：
5.1
通讯作者：
Chen, Gang
中科院分区：
文献类型：
--
作者：
Cui, Yonghua;Duan, Xiaochun;Chen, Gang
越来越多的研究表明硫化氢（H2S）在中枢神经系统（CNS）疾病中具有神经保护作用。然而，硫化氢在蛛网膜下腔出血（SAH）治疗中的潜在应用价值尚不清楚。本研究旨在探讨H2S对SAH所致早期脑损伤（EBI）的影响及其机制。在体内和体外研究了H2S供体硫氢化钠（NaHS）在SAH诱导的EBI中的作用。采用视交叉前池单次注射法建立实验性SAH动物模型。在体外培养的原代大鼠皮层神经元和人脐静脉内皮细胞（HUVECs）暴露于浓度为10 μM的OxyHb以模拟SAH。SAH明显抑制脑内内源性H2S的产生。SAH也相应地降低了脑中主要H2S生成酶的蛋白水平，包括胱硫醚合成酶（CBS）和3-巯基丙酮酸硫转移酶（3 MST），而NaHS处理恢复了H2S的产生以及CBS和3 MST的表达。更重要的是，NaHS治疗可以显着减轻SAH后的EBI（包括脑水肿，血脑屏障破坏，脑细胞凋亡，炎症反应和脑血管痉挛）。在体外，H2S通过作为抗氧化剂和抗凋亡介质来保护神经元和内皮功能。我们的研究结果表明，NaSH作为外源性H2S供体可以显着减少SAH诱导的EBI。
Increasing studies have demonstrated the neuroprotective effect of hydrogen sulfide (H2S) in central nervous system (CNS) diseases. However, the potential application value of H2S in the therapy of subarachnoid hemorrhage (SAH) is still not well known. This study was to investigate the potential effect of H2S on early brain injury (EBI) induced by SAH and explore the underlying mechanisms. The role of sodium hydrosulfide (NaHS), a donor of H2S, in SAH-induced EBI, was investigated in both in vivo and in vitro. A prechiasmatic cistern single injection model was used to produce experimental SAH in vivo. In vitro, cultured primary rat cortical neurons and human umbilical vein endothelial cells (HUVECs) were exposed to OxyHb at concentration of 10 μM to mimic SAH. Endogenous production of H2S in the brain was significantly inhibited by SAH. The protein levels of the predominant H2S-generating enzymes in the brain, including cystathionineb-synthase (CBS) and 3-mercaptopyruvate sulfur transferase (3MST), were also correspondingly reduced by SAH, while treatment with NaHS restored H2S production and the expressions of CBS and 3MST. More importantly, NaHS treatment could significantly attenuate EBI (including brain edema, blood–brain barrier disruption, brain cell apoptosis, inflammatory response, and cerebral vasospasm) after SAH. In vitro, H2S protects neurons and endothelial function by functioning as an antioxidant and antiapoptotic mediator. Our results suggest that NaSH as an exogenous H2S donor could significantly reduce EBI induced by SAH.