Hypoxia Augments Cerebral Inflammation in a Dextran Sulfate Sodium-Induced Colitis Mouse Model.

Hypoxia Augments Cerebral Inflammation in a Dextran Sulfate Sodium-Induced Colitis Mouse Model.
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缺氧加剧右旋糖酐硫酸钠诱导的结肠炎小鼠模型的脑炎症

DOI:
10.3389/fncel.2020.611764
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发表时间:
2020
影响因子:
5.3
通讯作者:
Zhu L
Zhu L
中科院分区:
医学2区
文献类型:
--
作者:
Han Y;Ding L;Cheng X;Zhao M;Zhao T;Guo L;Li X;Geng Y;Fan M;Liao H;Zhu L

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缺氧在炎症性肠病(IBD)病理生理学中的重要性越来越被认识到;此外,缺氧似乎是脑炎症的重要加速器,正如我们小组和其他人所报道的那样。IBD是一种慢性肠道疾病,导致炎症的发展,这与脑功能障碍有关。然而,没有研究报道缺氧是否与IBD诱导的神经炎症相关。因此,本研究的目的是确定缺氧是否会增加DSS诱导的结肠炎小鼠模型的脑炎症。使用3%DSS持续5天结合暴露于缺氧条件(6,000 m)持续2天来开发小鼠模型。将小鼠随机分为对照组、DSS组、缺氧组和DSS+缺氧组。结果表明,DSS结合缺氧导致结肠和血浆促炎细胞因子的上调。同时,DSS加缺氧增加了小胶质细胞活化标志物Iba 1的表达,并伴随着脑中肿瘤坏死因子-α(TNF-α)、白细胞介素-1 β(IL-1β)和白细胞介素-6(IL-6)的表达增加。此外,紧密连接蛋白,如紧密连接蛋白-1(ZO-1),闭合蛋白,和claudin-5的表达,显着下调。目前的研究为DSS诱导的结肠炎模型中缺氧暴露如何诱导大脑中过度的炎症反应和病理生理后果提供了新的见解。
The importance of hypoxia in the pathophysiology of inflammatory bowel disease (IBD) is increasingly being realized; also, hypoxia seems to be an important accelerator of brain inflammation, as has been reported by our group and others. IBD is a chronic intestinal disorder that leads to the development of inflammation, which is related to brain dysfunction. However, no studies have reported whether hypoxia is associated with IBD-induced neuroinflammation. Therefore, the objective of the present study was to determine whether hypoxia augments cerebral inflammation in a DSS-induced colitis mouse model. The mouse model was developed using 3% DSS for five days combined with exposure to hypoxic conditions (6,000 m) for two days. Mice were randomly divided into four groups: control group, DSS group, hypoxia group, and DSS plus hypoxia group. The results demonstrated that DSS combined with hypoxia resulted in up-regulation of colonic and plasmatic proinflammatory cytokines. Meanwhile, DSS plus hypoxia increased expression of Iba1, which is a marker of activated microglia, accompanied by increased expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the brain. Moreover, the expression of tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-5, was markedly downregulated. The current study provides new insight into how hypoxia exposure induces excessive inflammatory responses andpathophysiological consequences in the brain in a DSS-induced colitis model.
DOI: 10.1155/2016/3475356
发表时间: 2016
期刊: Evidence-based complementary and alternative medicine : eCAM
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期刊: IMMUNOBIOLOGY
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