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硫化氢预处理减轻小鼠短暂性大脑中动脉闭塞模型的脑缺血/再灌注损伤。

Preconditioning with hydrogen sulfide ameliorates cerebral ischemia/reperfusion injury in a mouse model of transient middle cerebral artery occlusion.

机构信息

Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, Shaanxi, China.

Department of Anesthesiology, Third Hospital of Xi'an, Xi'an, 710018, Shaanxi, China.

出版信息

Chem Biol Interact. 2019 Sep 1;310:108738. doi: 10.1016/j.cbi.2019.108738. Epub 2019 Jul 5.

Abstract

Ischemic stroke and reperfusion injury are a common and serve medical situation in the elderly population. HS is a gas neuromodulator which also possesses anti-oxidant and anti-inflammatory properties, and is found to play neuroprotective effect in neurodegenerative diseases. This study investigated the effect of endogenous and exogenous HS in a mouse model of ischemic stroke. 129P2-Cbs/J mice with heterozygous mutants in HS generating enzyme cystathionine β-synthase were used to study the effect of endogenous HS. HS donor NaHS was used as exogenous HS. Animals were pretreated with HS and then subjected to middle cerebral artery occlusion surgery. Behavioral outcome was evaluated by novel object recognition test. Inflammatory cytokines were measured using ELISA. Western blot was used to detect the activation of NF-κB. Aged 129P2-Cbs/J mice showed exaggerated inflammation and more severe cognitive impairment after ischemia, while exogenous HS treatment inhibited inflammation and attenuated behavioral impairment. The anti-inflammatory effect of HS was mediated by inhibiting NF-κB. Our findings suggest that both endogenous and exogenous HS are involved in the neuroprotection against ischemia/reperfusion-induced cerebral injury.

摘要

缺血性卒中和再灌注损伤是老年人群中常见且严重的医学情况。HS 是一种气体神经调节剂,具有抗氧化和抗炎特性,在神经退行性疾病中被发现具有神经保护作用。本研究探讨了内源性和外源性 HS 在缺血性卒中小鼠模型中的作用。使用胱硫醚β-合酶(HS 生成酶)杂合突变的 129P2-Cbs/J 小鼠研究内源性 HS 的作用。HS 供体 NaHS 用作外源性 HS。动物用 HS 预处理,然后进行大脑中动脉闭塞手术。通过新物体识别试验评估行为结果。使用 ELISA 测量炎性细胞因子。使用 Western blot 检测 NF-κB 的激活。老年 129P2-Cbs/J 小鼠在缺血后表现出炎症加剧和认知功能障碍更严重,而外源性 HS 治疗抑制了炎症并减轻了行为损伤。HS 的抗炎作用是通过抑制 NF-κB 介导的。我们的研究结果表明,内源性和外源性 HS 都参与了对缺血/再灌注引起的脑损伤的神经保护作用。

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