Bradykinin B2 Receptors Play a Neuroprotective Role in Hypoxia/reoxygenation Injury Related to Pyroptosis Pathway
Bradykinin B2 Receptors Play a Neuroprotective Role in Hypoxia/reoxygenation Injury Related to Pyroptosis Pathway
复制标题
缓激肽 B2 受体在与焦亡途径相关的缺氧/复氧损伤中发挥神经保护作用
DOI：
10.2174/1567202615666180528073141
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发表时间：
2018-01-01
影响因子：
2.1
通讯作者：
Zhu, Xiongchao
中科院分区：
文献类型：
--
作者：
Tang, Min;Li, Xia;Zhu, Xiongchao
背景：激肽是一种促炎肽，在组织损伤中介导许多血管和疼痛反应。激肽通过两种G蛋白偶联受体发挥其生物学功能：缓激肽1受体（B1 R）和缓激肽2受体（B2 R）。我们先前证明了在原代培养的皮层神经元缺氧/复氧（H/R）损伤后B2 R的上调。然而，B2受体在炎性小体诱导的pyroptosis的作用仍然unknow.Methods：我们诱导H/R神经元损伤的原代培养的皮层神经元收获胚胎第17天的大脑。接下来，我们使用annexin V FITC/碘化丙啶（PI）双染色技术研究了B2 R在H/R诱导的神经元凋亡或坏死中的神经保护功能。采用实时定量逆转录聚合酶链反应（RT-qPCR）和蛋白质印迹法检测细胞凋亡信号通路caspase-1、IL-1 β和IL-18的表达及GSDMD的表达，探讨其分子机制。
Background: Kinins are pro-inflammatory peptides that mediate numerous vascular and pain responses in tissue injury. Kinins exert their biological functions via two G-protein-coupled receptors: Bradykinin 1 Receptor (B1R) and Bradykinin 2 Receptor (B2R). We previously demonstrated the up-regulation of B2R after Hypoxia/Reoxygenation (H/R) injury in primary cultured cortical neurons. However, the role of B2R in inflammasome-induced pyroptosis remains unknown.Methods: We induced H/R neuronal injury in primary cultured cortical neurons harvested from embryonic day 17 brains. Next, we examined the neuroprotective function of B2R in H/R-induced neuronal apoptosis or necrosis using an annexin V FITC/Propidium Iodide (PI) double-staining technique. The pyroptosis signaling cascade, including caspase-1, IL-1 beta and IL-18 levels and Cleaved Gasdermin D (GSDMD) expression was examined by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting to explore the underlying molecular mechanism.Results: H/R injury significantly increased B2R protein expression (P