Shi Ligen, Liang Feng, Zheng Jingwei, Zhou Keren, Chen Sheng, Yu Jun, Zhang Jianmin
Department of Neurosurgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Brain Research Institute, Zhejiang University, Hangzhou, China.
Front Mol Neurosci. 2018 Mar 26;11:93. doi: 10.3389/fnmol.2018.00093. eCollection 2018.
Compelling evidence has indicated that imbalance between apoptosis and autophagy may be involved in subarachnoid hemorrhage (SAH). We aimed to investigate the effects and mechanisms of melatonin in the homeostasis of apoptosis and autophagy. One-hundred and forty-eight male Sprague-Dawley rats were intraperitoneally injected with melatonin or vehicle 2 h after SAH induction. Western blotting and an immunofluorescent assay were performed to detect the expression of apoptosis- and autophagy-related proteins. The neuroprotective effect of melatonin attenuating SAH-induced neurological deficit and brain edema may be associated with the suppression of SAH-induced neuronal apoptosis and autophagy. Furthermore, melatonin inhibited the cleavage of mammalian sterile 20-like kinase 1 (MST1) protein by reducing reactive oxygen species (ROS) content. These effects of melatonin on regulating the homeostasis between apoptosis and autophagy could be reversed by an MST1 agonist, chelerythrine, via enhancement of MST1 cleavage. In conclusion, exogenous melatonin alleviates SAH-induced early brain injury (EBI) by suppressing excessive neuronal apoptosis and autophagy. The underlying mechanism may, at least in part, involve the ROS-MST1 pathway.
有力证据表明，细胞凋亡与自噬之间的失衡可能与蛛网膜下腔出血（SAH）有关。我们旨在研究褪黑素在细胞凋亡和自噬稳态中的作用及机制。148只雄性Sprague-Dawley大鼠在SAH诱导后2小时腹腔注射褪黑素或赋形剂。采用蛋白质免疫印迹法和免疫荧光分析法检测细胞凋亡和自噬相关蛋白的表达。褪黑素减轻SAH诱导的神经功能缺损和脑水肿的神经保护作用可能与抑制SAH诱导的神经元细胞凋亡和自噬有关。此外，褪黑素通过降低活性氧（ROS）含量抑制哺乳动物不育20样激酶1（MST1）蛋白的裂解。MST1激动剂白屈菜红碱可通过增强MST1裂解来逆转褪黑素对细胞凋亡和自噬之间稳态的调节作用。总之，外源性褪黑素通过抑制过度的神经元细胞凋亡和自噬减轻SAH诱导的早期脑损伤（EBI）。其潜在机制可能至少部分涉及ROS-MST1途径。
