NaHS restores mitochondrial function and inhibits autophagy by activating the PI3K/Akt/mTOR signalling pathway to improve functional recovery after traumatic brain injury
NaHS restores mitochondrial function and inhibits autophagy by activating the PI3K/Akt/mTOR signalling pathway to improve functional recovery after traumatic brain injury
复制标题
NaHS通过激活PI3K/Akt/mTOR信号通路恢复线粒体功能并抑制自噬，改善脑外伤后功能恢复
DOI：
10.1016/j.cbi.2018.02.028
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发表时间：
2018-04-25
影响因子：
5.1
通讯作者：
Zhang, Hongyu
中科院分区：
文献类型：
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作者：
Xu, Kebin;Wu, Fangfang;Zhang, Hongyu
创伤性脑损伤（TBI）是世界上最严重的公共卫生问题之一。TBI通过触发继发性损伤导致神经功能缺损。硫化氢（H2S）是一种气体介质，据报道在中枢神经系统疾病（如TBI）中发挥神经保护作用。然而，参与这种效应的分子机制仍不清楚。本研究旨在探讨NaHS（一种H2S供体）在TBI小鼠模型中提供神经保护的能力，并发现这些保护作用的相关分子机制。在这里，我们发现，NaHS的管理不仅保持血脑屏障（BBB）的完整性，保护神经元免于凋亡，促进髓鞘再生和轴突修复，而且保护线粒体功能。此外，我们发现TBI后用NaHS处理后，自噬被抑制，这是由PI 3 K/AKT/mTOR信号通路激活诱导的效果。我们的研究表明H2S治疗对TBI有益，指出H2S是治疗TBI的潜在治疗靶点。
Traumatic brain injury (TBI) is one of the most serious public health problems in the world. TBI causes neurological deficits by triggering secondary injuries. Hydrogen sulfide (H2S), a gaseous mediator, has been reported to exert neuroprotective effects in central nervous system diseases, such as TBI. However, the molecular mechanisms involved in this effect are still unclear. The present study was designed to explore the ability of NaHS, a H2S donor, to provide neuroprotection in a mouse model of TBI and to discover the associated molecular mechanisms of these protective effects. Here, we found that administration of NaHS not only maintained the integrity of the blood brain barrier (BBB), protected neurons from apoptosis, and promoted remyelination and axonal reparation but also protected mitochondrial function. In addition, we found that autophagy was inhibited after treatment with NaHS following TBI, an effect that was induced by activation of the PI3K/AKT/mTOR signalling pathway. Our study indicated that H2S treatment is beneficial for TBI, pointing to H2S as a potential therapeutic target for treating TBI.