Hydrogen sulfide attenuates brain edema in early brain injury after subarachnoid hemorrhage in rats: Possible involvement of MMP-9 induced blood-brain barrier disruption and AQP4 expression
Hydrogen sulfide attenuates brain edema in early brain injury after subarachnoid hemorrhage in rats: Possible involvement of MMP-9 induced blood-brain barrier disruption and AQP4 expression
复制标题
硫化氢减轻大鼠蛛网膜下腔出血后早期脑损伤的脑水肿：可能与 MMP-9 诱导的血脑屏障破坏和 AQP4 表达有关
DOI：
10.1016/j.neulet.2016.04.018
复制
发表时间：
2016-05-16
影响因子：
2.5
通讯作者：
Chen, Gao
中科院分区：
文献类型：
--
作者：
Cao, Shenglong;Zhu, Ping;Chen, Gao
目标：方法：将96只雄性大鼠随机分为4组：假手术组（Sham）、SAH +溶媒组（Vehicle）、SAH +低剂量NaHS组（NaHS + Low Dose）和SAH +高剂量NaHS组（NaHS + High Dose）。结果：H2S可明显减轻SAH急性期脑水肿形成和细胞凋亡，改善神经功能障碍。H2S对脑水肿的影响可能与其抑制血脑屏障的破坏和减少星形胶质细胞APQ 4的表达有关。详细地说，H2S通过抑制MMP-9诱导的紧密连接蛋白（TJPs）降解来防止BBB破坏。H2S通过抑制胶质细胞活化和促炎性细胞因子分泌下调星形胶质细胞AQP 4表达。结论：H2S通过降低MMP-9表达活性抑制TJPs降解，通过抑制胶质细胞活化和促炎性细胞因子分泌抑制AQP 4表达，减轻脑水肿形成。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Aims: This study investigated the effect of H2S on brain edema formation and the possible underlying mechanisms in early brain injury (EBI) of SAH using the endovascular perforation model.Methods: 96 male rats were randomly divided into four groups: sham group, SAH + vehicle group, SAH + low-dosage NaHS group, and SAH + high-dosage NaHS group. Brain samples were used for brain water content and blood-brain barrier (BBB) leakage measurement, gelatin zymography, Western blot and immunohistochemistry.Results: H2S markedly attenuated brain edema formation and apoptotic cell death, improved neurological dysfunction in the acute stage of SAH. The possible mechanisms of H2S's effect on brain edema formation were through preventing BBB disruption and reducing APQ4 expression on astrocytes. In detail, H2S prevented BBB disruption by inhibiting MMP-9 induced tight junction proteins (TJPs) degradation. H2S down-regulated AQP4 expression on astrocytes by suppressing glial cell activation and pro-inflammatory cytokines secretion.Conclusion: Taken together, this study showed that H2S attenuated brain edema formation partially by inhibiting the degradation of TJPs via reducing MMP-9 expression activity and suppressing AQP4 expression via alleviating glia activation and pro-inflammatory cytokines secretion. (C) 2016 Elsevier Ireland Ltd. All rights reserved.