Neuroprotective Effect of Hydrogen-Rich Saline in Global Cerebral Ischemia/Reperfusion Rats: Up-Regulated Tregs and Down-Regulated miR-21, miR-210 and NF-κB Expression.

Neuroprotective Effect of Hydrogen-Rich Saline in Global Cerebral Ischemia/Reperfusion Rats: Up-Regulated Tregs and Down-Regulated miR-21, miR-210 and NF-κB Expression.
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富氢盐水对全脑缺血/再灌注大鼠的神经保护作用:上调 Tregs 和下调 miR-21、miR-210 和 NF-kappaB 表达。

DOI:
10.1007/s11064-016-1978-x
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发表时间:
2016-10
影响因子:
4.4
通讯作者:
Sun, Xuejun
Sun, Xuejun
中科院分区:
医学3区
文献类型:
--
作者:
Li, Qian;Yu, Pan;Zeng, Qiuting;Luo, Bing;Cai, Shenquan;Hui, Kangli;Yu, Gao;Zhu, Changsong;Chen, Xingdong;Duan, Manlin;Sun, Xuejun

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最近,有人提出,氢分子(H2)可以选择性地降低羟自由基(.OH)的水平,并改善全脑缺血再灌注模型中器官的氧化和炎症损伤。全脑缺血/再灌注(I/R)可诱导炎症细胞因子突然激活,随后影响全身免疫反应性,这可能导致更糟糕的结果。调节性 T 细胞 (Treg) 参与脑 I/R 的多个病理方面。此外,miRNA参与细胞对缺氧的反应过程。因为缺氧会上调一组称为“hypoxamirs”的特定 miRNA 的表达。因此,本研究的目的是分析HRS对I/R诱导的脑损伤、Tregs和特异性miRNA的影响。我们的结果表明,经历全脑 I/R 并接受 HRS 治疗的大鼠比未经 HRS 治疗的 I/R 动物损伤更轻。 I/R组再灌注后6、24和96 h各时间点海马中miR-210表达量均显着升高,而HRS治疗组其表达量显着降低。此外,I/R 组的 Tregs 数量在每个时间点均减少,而 HRS 治疗组的 Tregs 数量在再灌注后 24 小时和 96 小时有所增加。我们重点关注24小时Tregs、TGF-β1、TNF-α和NF-κB之间的关系,发现它们之间存在高度相关性。因此,我们的结果表明,HRS治疗大鼠的脑复苏机制可能与上调Treg细胞数量的作用有关。
Recently, it has been suggested that molecular hydrogen (H2) can selectively reduce the levels of hydroxyl radicals (.OH), and ameliorate oxidative and inflammatory injuries to organs in global cerebral ischemia reperfusion models. Global cerebral ischemia/reperfusion (I/R) can induce a sudden activation of inflammatory cytokines and later influence the systemic immunoreactivity which may contribute to a worse outcome. Regulatory T cells (Tregs) are involved in several pathological aspects of cerebral I/R. In addition, miRNA took part in the processes of cellular response to hypoxia. Since the expression of a specific set of miRNA called “hypoxamirs” is upregulated by hypoxia. Therefore, the aim of this study was to analyze the effect of HRS on I/R inducing cerebral damage, Tregs, and specific miRNA. Our results showed that rats undergone global cerebral I/R and treated with HRS have milder injury than I/R animals without HRS treatment. miR-210 expression in the hippocampus of the I/R group at 6, 24 and 96 h after reperfusion was significantly increased at each time point, while its expression in the group treated with HRS was significantly decreased. In addition, Tregs number in group I/R was decreased at each time points, while its number in the group treated with HRS was increased at 24 and 96 h after reperfusion. We focus on the relationship among Tregs, TGF-β1, TNF-α and NF-κB at 24 h, and we found that there is a high correlation among them. Therefore, our results indicated that the brain resuscitation mechanism in the HRS-treated rats may be related with the effect of upregulating the number of Treg cells.
DOI: 10.4161/cc.9.6.11006
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