Hydrogen sulfide as the third endogenous gaseous mediator had protective effects against traumatic brain injury-induced neuronal damage in mice. However, the exact pathophysiological mechanism underlying traumatic brain injury is complicated and the protective role of H₂S is not yet fully known. Therefore, we combined the mechanical injury (scratch) with secondary injury including metabolic impairment (no glucose) together to investigate the underlying cellular mechanism of hydrogen sulfide in vitro models of traumatic brain injury. In the present study, we found that H₂S could prevent the scratch-induced decrease in the expression of cystathionine-β-synthetase, a key enzyme involved in the source of hydrogen sulfide, and endogenous hydrogen sulfide generation in PC12 cells. We also found that hydrogen sulfide could prevent scratch-induced cellular injury, alteration of mitochondrial membrane potential, intracellular accumulation of reactive oxygen species and cell death (autophagic cell death and apoptosis) in PC12 cells. It was also found that blocking PI3K/AKT pathway by LY294002, abolished the protection of H₂S against scratch-induced cellular reactive oxygen species level and NRF2 accumulation and function in the nucleus. These results suggest that hydrogen sulfide protects against cell damage induced by scratch injury through modulation of the PI3K/Akt/Nrf2 pathway. This study raises the possibility that hydrogen sulfide may have therapeutic efficacy in traumatic brain injury.

硫化氢作为第三种内源性气态介质，对小鼠脑外伤引起的神经元损伤具有保护作用。但是，创伤性脑损伤的确切病理生理机制复杂，并且H ₂ S的保护作用尚不完全清楚。因此，我们将机械性损伤（从头开始）与包括代谢性损伤（无葡萄糖）在内的继发性损伤相结合，共同研究了硫化氢在脑外伤模型中的潜在细胞机制。在本研究中，我们发现H ₂S可以防止刮擦诱导的胱硫醚-β合成酶的表达下降，胱甘肽-β合成酶是参与硫化氢来源的关键酶，以及PC12细胞内源性硫化氢的产生。我们还发现，硫化氢可以预防PC12细胞中由刮擦引起的细胞损伤，线粒体膜电位的改变，细胞内活性氧的积累以及细胞死亡（自噬细胞死亡和凋亡）。还发现LY294002阻断PI3K / AKT通路，取消了对H ₂的保护。S对抗划痕诱导的细胞活性氧水平和NRF2在核中的积累和功能。这些结果表明，硫化氢可通过调节PI3K / Akt / Nrf2途径来防止刮擦损伤引起的细胞损伤。这项研究提出了硫化氢在颅脑外伤中可能具有治疗功效的可能性。