Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2-related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning
Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2-related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning
复制标题
DOI：
10.1097/aln.0000000000001485
复制
发表时间：
2017-03-01
期刊：
影响因子：
8.8
通讯作者：
Dong, Hailong
中科院分区：
文献类型：
--
作者：
Cai, Min;Tong, Li;Dong, Hailong
背景：抗氧化作用在挥发性麻醉药的神经保护作用中起重要作用。越来越多的证据表明，核因子E2相关因子2可通过多种途径上调内源性抗氧化作用。然而，是否核因子E2相关因子2的激活调制七氟烷预处理，如果是这样的话，什么是这种activation.Methods的上游信号级联反应的基础仍然是未知的：七氟烷（2.5%），每天1小时，连续5天在小鼠七氟烷预处理。采用大脑中动脉闭塞法造成局灶性脑缺血再灌注损伤。检测核因子E2相关因子2、Kelch样ECH相关蛋白1、锰超氧化物歧化酶、硫氧还蛋白-1和烟酰胺腺嘌呤二核苷酸磷酸喹诺酮氧化还原酶-1的表达（n = 6）。还检测了抗氧化活性和氧化产物表达。为了确定kelch样ECH相关蛋白1抑制依赖性核因子-E2相关因子2激活在七氟烷预处理诱导的神经保护中的作用，通过核因子-E2相关因子2敲除、kelch样ECH相关蛋白1过表达慢病毒，Kelch样ECH相关蛋白1缺陷型小干扰RNA（n = 8）。梗死体积，神经功能评分和细胞凋亡进行了assessed.Results：七氟烷预处理引起神经保护和增加核因子E2相关因子2核转位，这反过来又上调内源性抗氧化和减少氧化损伤。七氟醚预处理减少Kelch样ECH相关蛋白1的表达。核因子E2相关因子2消融通过介导抗氧化剂的上调而取消神经保护并逆转七氟烷预处理。Kelch样ECH相关蛋白1过表达逆转了核因子E2相关因子2的上调，并取消了七氟醚预处理诱导的神经保护作用。Kelch-like ECH-associated protein 1 small interfering RNA administration improved nuclear factor-E2-related factor 2 expression and the outcome of mice subjected to ischemia/reperfusion injury.Conclusions：Kelch-like ECH-associated protein 1 downregulation-dependent nuclear factor-E2-related factor 2 activation underlies the ability of sevoflurane preconditioning to activate the endogenous antioxidant response，which elevently its neuroprotection.
Background: The authors have reported that antioxidative effects play a crucial role in the volatile anesthetic-induced neuroprotection. Accumulated evidence shows that endogenous antioxidation could be up-regulated by nuclear factorE2- related factor 2 through multiple pathways. However, whether nuclear factor-E2-related factor 2 activation is modulated by sevoflurane preconditioning and, if so, what is the signaling cascade underlying upstream of this activation are still unknown.Methods: Sevoflurane preconditioning in mice was performed with sevoflurane (2.5%) 1 h per day for five consecutive days. Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. Expression of nuclear factor-E2-related factor 2, kelch-like ECH-associated protein 1, manganese superoxide dismutase, thioredoxin-1, and nicotinamide adenine dinucleotide phosphate quinolone oxidoreductase-1 was detected (n = 6). The antioxidant activities and oxidative product expression were also examined. To determine the role of kelch-like ECH-associated protein 1 inhibition-dependent nuclear factor-E2-related factor 2 activation in sevoflurane preconditioning-induced neuroprotection, the kelch-like ECH-associated protein 1-nuclear factor-E2-related factor 2 signal was modulated by nuclear factor-E2-related factor 2 knockout, kelch-like ECH-associated protein 1 overexpression lentivirus, and kelch-like ECH-associated protein 1 deficiency small interfering RNA (n = 8). The infarct volume, neurologic scores, and cellular apoptosis were assessed.Results: Sevoflurane preconditioning elicited neuroprotection and increased nuclear factor-E2-related factor 2 nuclear translocation, which in turn up-regulated endogenous antioxidation and reduced oxidative injury. Sevoflurane preconditioning reduced kelch-like ECH-associated protein 1 expression. Nuclear factor-E2-related factor 2 ablation abolished neuroprotection and reversed sevoflurane preconditioning by mediating the up-regulation of antioxidants. Kelch-like ECH-associated protein 1 overexpression reversed nuclear factor-E2-related factor 2 up-regulation and abolished the neuroprotection induced by sevoflurane preconditioning. Kelch-like ECH-associated protein 1 small interfering RNA administration improved nuclear factor-E2-related factor 2 expression and the outcome of mice subjected to ischemia/reperfusion injury.Conclusions: Kelch-like ECH-associated protein 1 down-regulation-dependent nuclear factor-E2-related factor 2 activation underlies the ability of sevoflurane preconditioning to activate the endogenous antioxidant response, which elicits its neuroprotection.