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首页> 外文期刊>BMC Neuroscience >Neuroprotective dobutamine treatment upregulates superoxide dismutase 3, anti-oxidant and survival genes and attenuates genes mediating inflammation
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Neuroprotective dobutamine treatment upregulates superoxide dismutase 3, anti-oxidant and survival genes and attenuates genes mediating inflammation

机译:神经保护性多巴酚丁胺治疗上调超氧化物歧化酶3,抗氧化剂和存活基因,并减弱介导炎症的基因

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Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The beta1-adrenergic agonist dobutamine protects against hypoxia/aglycemia induced neuronal damage. We aimed to identify the associated protective biological processes involved. Hippocampal slices from 6?days old mice showed significant changes of gene expression comparing slices with or without dobutamine (50?mM) in the following two experimental paradigms: (1) control conditions versus lipopolysacharide (LPS) stimulation and (2) oxygen–glucose deprivation (OGD), versus combined LPS/OGD. Dobutamine depressed the inflammatory response by modifying the toll-like receptor-4 signalling pathways, including interferon regulatory factors and nuclear factor κ B activation in experimental paradigm 1. The anti-oxidant defense genes superoxide dismutase 3 showed an upregulation in the OGD paradigm while thioredoxin reductase was upregulated in LPS paradigm. The survival genes Bag-3, Tinf2, and TMBIM-1, were up-regulated in paradigm 1. Moreover, increased levels of SOD3 were verified on the protein level 24?h after OGD and control stimulation in cultures with or without preconditioning with LPS and dobutamine, respectively. Neuroprotective treatment with dobutamine depresses expression of inflammatory mediators and promotes the defense against oxidative stress and depresses apoptotic genes in a model of neonatal brain hypoxia/ischemia interpreted as pharmacological preconditioning. We conclude that beta1-adrenoceptor activation might be an efficient strategy for identifying novel pharmacological targets for protection of the neonatal brain.
机译:人工分娩会使胎儿遭受缺氧发作并伴有肾上腺调节儿茶酚胺激增,可能提供针对缺氧性损伤的保护。 β1肾上腺素能激动剂多巴酚丁胺可防止缺氧/血糖过低引起的神经元损伤。我们旨在确定涉及的相关保护性生物过程。在以下两个实验范式中,与有或没有多巴酚丁胺(50?mM)的切片相比,来自6?日龄小鼠的海马切片显示出显着的基因表达变化:(1)对照条件与脂多糖(LPS)刺激和(2)氧葡萄糖剥夺(OGD),而不是合并的LPS / OGD。多巴酚丁胺通过修饰实验范式1中的toll样受体4信号传导途径(包括干扰素调节因子和核因子κB活化)来抑制炎症反应。抗氧化防御基因超氧化物歧化酶3在OGD范式中表达上调,而硫氧还蛋白则LPS范式中还原酶上调。生存基因Bag-3,Tinf2和TMBIM-1在范例1中上调。此外,在有或没有LPS预处理的培养物中,OGD后24?h蛋白质水平上的SOD3水平增加,并控制了刺激和多巴酚丁胺。用多巴酚丁胺进行的神经保护性治疗在被解释为药理学预处理的新生儿脑缺氧/缺血模型中,抑制了炎症介质的表达并促进了对氧化应激的防御,并抑制了凋亡基因。我们得出的结论是,β1肾上腺素受体激活可能是一种有效的策略,用于识别保护新生儿脑的新型药理靶标。

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