Kinin B1 Receptor Mediates Bidirectional Interaction between Neuroinflammation and Oxidative Stress.

Kinin B1 Receptor Mediates Bidirectional Interaction between Neuroinflammation and Oxidative Stress.
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Kinin B1受体介导神经炎症和氧化应激之间的双向相互作用。

DOI:
10.3390/antiox12010150
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发表时间:
2023-01-08
期刊:
Antioxidants (Basel, Switzerland)
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其他
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高血压与神经元内激肽 B1 受体 (B1R) 表达增加和促炎细胞因子水平增加有关。我们之前报道,血管紧张素 II (Ang II) 上调 B1R 表达,并可诱导初级下丘脑神经元的神经炎症和氧化应激。然而,B1R 激活、神经炎症和氧化应激发生的顺序尚未研究。使用新生小鼠的原代下丘脑神经元,我们发现肿瘤坏死因子 (TNF)、脂多糖 (LPS) 和过氧化氢 (H2O2) 可以上调 B1R 表达并增加氧化应激。此外,我们的研究表明,用 R715(一种特定的 B1R 拮抗剂)阻断 B1R 可以减弱这些影响。为了进一步证实我们的发现,我们使用了醋酸脱氧皮质酮(DOCA)盐模型来表明大脑下丘脑室旁核(PVN)中的氧化应激上调。总之,这些数据提供了新的证据,证明大脑中氧化应激、神经炎症和 B1R 上调之间的关系是双向的,并且 B1R 拮抗可能对各种疾病病理中的神经炎症和氧化应激产生有益影响。
Hypertension is associated with increased expression of kinin B1 receptors (B1R) and increased levels of pro-inflammatory cytokines within the neurons. We previously reported that angiotensin II (Ang II) upregulates B1R expression and can induce neuroinflammation and oxidative stress in primary hypothalamic neurons. However, the order in which B1R activation, neuroinflammation, and oxidative stress occur has not yet been studied. Using primary hypothalamic neurons from neonatal mice, we show that tumor necrosis factor (TNF), lipopolysaccharides (LPS), and hydrogen peroxide (H2O2) can upregulate B1R expression and increase oxidative stress. Furthermore, our study shows that B1R blockade with R715, a specific B1R antagonist, can attenuate these effects. To further confirm our findings, we used a deoxycorticosterone acetate (DOCA)-salt model of hypertension to show that oxidative stress is upregulated in the hypothalamic paraventricular nucleus (PVN) of the brain. Together, these data provide novel evidence that relationship between oxidative stress, neuroinflammation, and B1R upregulation in the brain is bidirectional, and that B1R antagonism may have beneficial effects on neuroinflammation and oxidative stress in various disease pathologies.
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