Yu Qian, Wang Binrong, Zhao Tianzhi, Zhang Xiangnan, Tao Lei, Shi Jinshan, Sun Xude, Ding Qian
Department of Anesthesiology, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University Xi'an, China.
Front Cell Neurosci. 2017 Mar 7;11:67. doi: 10.3389/fncel.2017.00067. eCollection 2017.
Brain ischemia leads to poor oxygen supply, and is one of the leading causes of brain damage and/or death. Neuroprotective agents are thus in great need for treatment purpose. Using both young and aged primary cultured hippocampal neurons as models, we investigated the effect of sodium hydrosulfide (NaHS), an exogenous donor of hydrogen sulfide, on oxygen-glucose deprivation (OGD) damaged neurons that mimick focal cerebral ischemia/reperfusion (I/R) induced brain injury. NaHS treatment (250 μM) protected both young and aged hippocampal neurons, as indicated by restoring number of primary dendrites by 43.9 and 68.7%, number of dendritic end tips by 59.8 and 101.1%, neurite length by 36.8 and 66.7%, and spine density by 38.0 and 58.5% in the OGD-damaged young and aged neurons, respectively. NaHS treatment inhibited growth-associated protein 43 downregulation, oxidative stress in both young and aged hippocampal neurons following OGD damage. Further studies revealed that NaHS treatment could restore ERK1/2 activation, which was inhibited by OGD-induced protein phosphatase 2 (PP2A) upregulation. Our results demonstrated that NaHS has potent protective effects against neuron injury induced by OGD in both young and aged hippocampal neurons.
脑缺血会导致氧气供应不足，是脑损伤和/或死亡的主要原因之一。因此，治疗上急需神经保护剂。我们以年轻和老年原代培养海马神经元为模型，研究了外源性硫化氢供体硫氢化钠（NaHS）对模拟局灶性脑缺血/再灌注（I/R）诱导脑损伤的氧-葡萄糖剥夺（OGD）损伤神经元的影响。NaHS处理（250μM）对年轻和老年海马神经元均有保护作用，表现为在OGD损伤的年轻和老年神经元中，初级树突数量分别恢复43.9%和68.7%，树突末梢数量分别恢复59.8%和101.1%，神经突长度分别恢复36.8%和66.7%，棘密度分别恢复38.0%和58.5%。NaHS处理抑制了OGD损伤后年轻和老年海马神经元中生长相关蛋白43的下调以及氧化应激。进一步研究表明，NaHS处理可恢复被OGD诱导的蛋白磷酸酶2（PP2A）上调所抑制的ERK1/2激活。我们的结果表明，NaHS对OGD诱导的年轻和老年海马神经元损伤具有强大的保护作用。
