Electroacupuncture attenuated cerebral ischemic injury and neuroinflammation through α7nAChR-mediated inhibition of NLRP3 inflammasome in stroke rats
Electroacupuncture attenuated cerebral ischemic injury and neuroinflammation through α7nAChR-mediated inhibition of NLRP3 inflammasome in stroke rats
复制标题
电针对中风大鼠通过α7nAChR介导的NLRP3炎症小体抑制作用减轻脑缺血损伤和神经炎症
DOI：
10.1186/s10020-019-0091-4
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发表时间：
2019-05-22
影响因子：
5.7
通讯作者：
Wang, Qiang
中科院分区：
文献类型：
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作者：
Jiang, Tao;Wu, Meiyan;Wang, Qiang
背景：我们之前的研究证实，电针（EA）刺激通过7烟碱型乙酰胆碱受体（α7nAChR）介导的高迁移率基团box1释放机制的抑制作用，对脑缺血损伤产生神经保护作用。本研究探讨α7nAChR的信号转导和NLRP3炎性小体的抑制是否参与电针刺激的神经保护作用。方法：在成年雄性Sprague-Dawley大鼠中，采用大脑中动脉闭塞（MCAO）模型诱导1.5小时局灶性脑缺血损伤。通过蛋白质印迹和免疫荧光染色评估再灌注后半影组织中 NLRP3 炎症小体的表达。再灌注72h后，在存在或不存在α7nAChR拮抗剂（α-BGT）或激动剂（PHA-543,613）的情况下，评估梗死面积、神经功能缺损评分、TUNEL染色以及促炎因子或抗炎细胞因子的表达。结果：脑缺血/再灌注（I/R）后炎症小体蛋白的含量逐渐增加。电针刺激减弱NLRP3炎症小体介导的炎症反应并调节促炎因子和抗炎细胞因子之间的平衡。 α7nAChR 激动剂诱导与 EA 刺激相似的神经保护作用。相比之下，α7nAChR拮抗剂不仅可以逆转神经保护作用，还可以逆转NLRP3炎症小体的抑制作用以及对促炎因子和抗炎细胞因子之间平衡的调节作用。这些结果提供了令人信服的证据，证明α7nAChR在调节脑缺血再灌注后神经元中NLRP3炎症小体的激活和表达中发挥着关键作用。这些发现强调了α7nAChR调节NLRP3炎症小体抑制的电针刺激的新抗炎机制，表明神经元中的7nAChR依赖性胆碱能抗炎系统和NLRP3炎症小体可能作为电针诱导的针对脑缺血性损伤的神经保护的潜在治疗靶点。
Background: Our previous research confirmed that electroacupuncture (EA) stimulus elicits neuroprotective effects against cerebral ischemic injury through 7 nicotinic acetylcholine receptor (alpha 7nAChR)-mediated inhibition of high-mobility group box1 release mechanism. This study investigated whether the signal transducer of alpha 7nAChR and inhibition of NLRP3 inflammasome are involved in the neuroprotective effects of EA stimulus.Methods: In adult male Sprague-Dawley rats, the focal cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO) models for 1.5 h. The expression of NLRP3 inflammasome in the penumbral tissue following reperfusion was assessed by western blotting and immunoflourescent staining. The infarct size, neurological deficit score, TUNEL staining and the expression of proinflammatory factors or anti-inflammatory cytokines were evaluated at 72h after reperfusion in the presence or absence of either alpha 7nAChR antagonist (alpha-BGT) or agonist (PHA-543,613).Results: The contents of inflammasome proteins were gradually increased after cerebral ischemia/reperfusion (I/R). EA stimulus attenuated NLRP3 inflammasome mediated inflammatory reaction and regulated the balance between proinflammatory factors and anti-inflammatory cytokines. The agonist of alpha 7nAChR induced similar neuroprotective effects as EA stimulus. In contrast, alpha 7nAChR antagonist reversed not only the neuroprotective effects, but also the inhibitory effects of NLRP3 inflammasome and the regulatory effects on the balance between proinflammatory factors and anti-inflammatory cytokines.Conclusions; These results provided compelling evidence that alpha 7nAChR played a pivotal role in regulating the activation and expression of NLRP3 inflammasome in neurons after cerebral I/R. These findings highlighted a novel anti-inflammatory mechanism of EA stimulus by alpha 7nAChR modulating the inhibition of NLRP3 inflammasome, suggesting that 7nAChR-dependent cholinergic anti-inflammatory system and NLRP3 inflammasome in neurons might act as potential therapeutic targets in EA induced neuroprotection against cerebral ischemic injury.