Shui Mengyang, Liu Xiaoyan, Zhu Yuanjun, Wang Yinye
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
Can J Physiol Pharmacol. 2016 Nov;94(11):1187-1192. doi: 10.1139/cjpp-2016-0100. Epub 2016 Jun 22.
Hydrogen sulfide (HS), the third gas transmitter, has been proven to be neuroprotective in cerebral ischemic injury, but whether its effect is mediated by regulating autophagy is not yet clear. The present study was undertaken to explore the underlying mechanisms of exogenous HS on autophagy regulation in cerebral ischemia. The effects and its connection with autophagy of NaHS, a HS donor, were observed through neurological deficits and cerebral infarct volume in middle cerebral artery occlusion (MCAO) mice; autophagy-related proteins and autophagy complex levels in the ischemic hemisphere were detected with Western blot assay. Compared with the model group, NaHS significantly decreased infarct volume and improved neurological deficits; rapamycin, an autophagy activator, abolished the effect of NaHS; NaHS decreased the expression of LC3-II and up-regulated p62 expression in the ischemic cortex 24 h after ischemia. However, NaHS did not significantly influence Beclin-1 expression. HS has a neuroprotective effect on ischemic injury in MCAO mice; this effect is associated with its influence in down-regulating autophagosome accumulation.
硫化氢（HS）作为第三种气体信号分子，已被证实在脑缺血损伤中具有神经保护作用，但其作用是否通过调节自噬介导尚不清楚。本研究旨在探讨外源性HS对脑缺血自噬调节的潜在机制。通过观察大脑中动脉闭塞（MCAO）小鼠的神经功能缺损和脑梗死体积，研究HS供体硫氢化钠（NaHS）的作用及其与自噬的关系；采用蛋白质免疫印迹法检测缺血半球自噬相关蛋白和自噬复合体水平。与模型组相比，NaHS显著减小梗死体积，改善神经功能缺损；自噬激活剂雷帕霉素可消除NaHS的作用；缺血24小时后，NaHS降低缺血皮层中LC3-II的表达并上调p62表达。然而，NaHS对Beclin-1表达无显著影响。HS对MCAO小鼠的缺血损伤具有神经保护作用；这种作用与其下调自噬体积累有关。
