Nodal mitigates cerebral ischemia-reperfusion injury via inhibiting oxidative stress and inflammation
Nodal mitigates cerebral ischemia-reperfusion injury via inhibiting oxidative stress and inflammation
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Nodal 通过抑制氧化应激和炎症减轻脑缺血再灌注损伤
DOI：
10.26355/eurrev_201907_18337
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发表时间：
2019-07-01
影响因子：
3.3
通讯作者：
Xu, Z-X
中科院分区：
文献类型：
--
作者：
Cui, Y.;Wang, J-Q;Xu, Z-X
目的：Nodal是转化生长因子β（TGF-β）家族的成员，其诱导细胞质Smad 2和Smad 3的活化，这两者都对脑缺血再灌注（I/R）损伤发挥神经保护作用。然而，Nodal在脑I/R中的作用尚不清楚。因此，本研究的目的是阐明Nodal在脑I/R injury.Materials AND Methods中的功能：脑I/R损伤诱导的Sprague道利（SD）大鼠大脑中动脉闭塞（MCAO）和再灌注和小鼠海马神经元细胞（HT 22）的氧-葡萄糖剥夺/再灌注（OGD/R）刺激。用慢病毒载体（Nodal过表达慢病毒载体[OE-Nodal]和Nodal短发RNA [sh-Nodal]）分别上调和下调SD大鼠或细胞Nodal表达。OE-Nodal能明显缩小脑梗死体积，抑制脑细胞凋亡。它还增加了超氧化物歧化酶（SOD），一种抗氧化酶的水平，并降低了脂质过氧化物（丙二醛[MDA]和乳酸脱氢酶[LDH]）的水平，以及促炎因子的水平。结论：Nodal通过抑制过度氧化应激和炎症反应，对脑缺血再灌注损伤具有保护作用。
OBJECTIVE: Nodal is a member of the transforming growth factor beta (TGF-beta) family, which induces the activation of the cytoplasmic Smad2 and Smad3, both of which play a neuroprotective role against cerebral ischemia-reperfusion (I/R) injury. However, the role of Nodal in cerebral I/R is unclear. Thus, the aim of the present study was to shed light on the function of Nodal in cerebral I/R injury.MATERIALS AND METHODS: Cerebral I/R injury was induced in the Sprague Dawley (SD) rats by middle cerebral artery occlusion (MCAO) and reperfusion and in murine hippocampal neuronal cells (HT22) by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The lentivirus vectors (Nodal overexpressing lentivirus vector [OE-Nodal] and the short hair RNA of Nodal [sh-Nodal]) were used to upregulate and downregulate Nodal in SD rats or cells.RESULTS: Nodal expression increased in the cerebral I/R models and reached a peak after 12 h of reperfusion. OE-Nodal administration to the cerebral I/R rats significantly reduced the cerebral infarction volume and inhibited the brain cell apoptosis. It also increased the level of superoxide dismutase (SOD), an antioxidant enzyme, and decreased the levels of the lipid peroxides (malondialdehyde [MDA] and lactate dehydrogenase [LDH]), in addition to those of the proinflammatory factors. Consistently, the upregulation of Nodal in HT22 by OGD/R significantly increased the SOD level and decreased the levels of MDA, LDH, interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha).CONCLUSIONS: This study revealed that Nodal exerted a protective role during cerebral I/R by inhibiting excessive oxidative stress and inflammation.