Synergistic protective effects of humanin and necrostatin-1 on hypoxia and ischemia/reperfusion injury.
Synergistic protective effects of humanin and necrostatin-1 on hypoxia and ischemia/reperfusion injury.
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护脑素和necrostatin-1对缺氧和缺血/再灌注损伤的协同保护作用
DOI：
10.1016/j.brainres.2010.07.080
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发表时间：
2010-10-08
期刊：
影响因子：
2.9
通讯作者：
Chua BH
中科院分区：
文献类型：
--
作者：
Xu X;Chua KW;Chua CC;Liu CF;Hamdy RC;Chua BH
由于脑缺血/再灌注损伤涉及几种不同的通路，因此可能需要联合治疗而不是单一治疗来获得有效的神经保护。在这项研究中，我们检测了凋亡抑制剂Gly14-humanin （HNG）和坏死性下垂抑制剂necrostatin-1 （Nec-1）对缺氧/缺血/再灌注损伤的保护作用。将培养的小鼠皮层原代神经元与Nec-1、HNG或同时在缺氧室中孵育60分钟。在氧葡萄糖剥夺（OGD）处理24 h后，采用MTS法测定细胞活力。小鼠大脑中动脉闭塞75 min，再灌注24 h。小鼠在再灌注后4 h给予HNG和/或Nec-1 （i.c.v）。通过TTC染色评估神经功能缺损，测定脑梗死体积。Nec-1或HNG单独对ogd诱导的细胞死亡具有保护作用。与Nec-1或HNG单独治疗相比，Nec-1和HNG联合治疗具有更强的神经保护作用。HNG或Nec-1治疗脑梗死体积分别从59.3±2.6%降至47.0±2.3%和47.1±1.5%。HNG和Nec-1联合治疗可改善神经学评分，并将梗死体积降低至38.6±1.5%。总之，我们证明了HNG和Nec-1联合治疗对体外和体内缺氧/缺血/再灌注损伤具有协同神经保护作用。这些发现为联合抗细胞凋亡和抗坏死下垂治疗脑卒中提供了一种新的治疗策略。
Since several different pathways are involved in cerebral ischemia/reperfusion injury, combination therapy rather than monotherapy may be required for efficient neuroprotection. In this study, we examined the protective effects of an apoptosis inhibitor Gly14-humanin (HNG) and a necroptosis inhibitor necrostatin-1 (Nec-1) on hypoxia/ischemia/reperfusion injury. Cultured mouse primary cortical neurons were incubated with Nec-1, HNG or both in a hypoxia chamber for 60 min. Cell viability was determined by MTS assay at 24 h after oxygen-glucose deprivation (OGD) treatment. Mice underwent middle cerebral artery occlusion for 75 min followed by 24 h reperfusion. Mice were administered HNG and/or Nec-1 (i.c.v.) at 4 h after reperfusion. Neurological deficits were evaluated and the cerebral infarct volume was determined by TTC staining. Nec-1 or HNG alone had protective effects on OGD-induced cell death. Combined treatment with Nec-1 and HNG resulted in more neuroprotection than Nec-1 or HNG alone. Treatment with HNG or Nec-1 reduced cerebral infarct volume from 59.3 ± 2.6% to 47.0 ± 2.3% and 47.1 ± 1.5%, respectively. Combined treatment with HNG and Nec-1 improved neurological scores and decreased infarct volume to 38.6 ± 1.5%. In summary, we demonstrated that the combination treatment of HNG and Nec-1 conferred synergistic neuroprotection on hypoxia/ischemia/reperfusion injury in vitro and in vivo. These findings provide a novel therapeutic strategy for the treatment of stroke by combining anti-apoptosis and anti-necroptosis therapy.
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8.3
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