Fu Chen, Zhang Xinyang, Zeng Zixiu, Tian Yang, Jin Xianglan, Wang Fengli, Xu Zhenmin, Chen Baoxin, Zheng Hong, Liu Xuemei
Central Laboratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China.
Department of Traditional Chinese Internal Medicine, Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2020 Feb 20;11:65. doi: 10.3389/fphar.2020.00065. eCollection 2020.
Ischemic stroke patients suffer from relatively limited treatment options. Studies have shown that in cerebral ischemia, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a key mediator in mediating inflammatory responses and results in activation of apoptosis signaling pathways. Here we assessed the and effects of Qingnao Dripping Pills (QNDP), a traditional Chinese prescription, on inflammatory responses and apoptosis. Our results showed that QNDP could significantly decrease cerebral ischemia injury, improve neurological function and inhibit apoptosis in rats impaired by middle cerebral artery occlusion (MCAO). Further, we found that QNDP inhibited NLRP3 inflammasome expression both in MCAO rats and in SH-SY5Y cells under OGD. Moreover, the levels of inflammatory cytokines including interleukin-1β (IL-1β) and IL-18, which mediated by NLRP3 inflammasome and increased in MCAO rats, could be reduced by QNDP, suggesting that QNDP could protect the neurons against inflammation through a mechanism mediated by NLRP3 inflammasome. Nuclear factor-kappa B (NF-κB) was also involved in the anti-inflammatory effect of QNDP. In conclusion, QNDP had neuroprotective effects against cerebral ischemia inhibiting NLRP3 inflammasome signaling pathway, and was a potential candidate for the future treatment of ischemic stroke.
缺血性中风患者的治疗选择相对有限。研究表明,在脑缺血中,含NOD样受体家族吡啉结构域蛋白3(NLRP3)炎性小体是介导炎症反应并导致凋亡信号通路激活的关键介质。在此,我们评估了中药复方清脑滴丸(QNDP)对炎症反应和凋亡的影响。我们的结果表明,QNDP可显著减轻大脑中动脉闭塞(MCAO)损伤大鼠的脑缺血损伤,改善神经功能并抑制细胞凋亡。此外,我们发现QNDP在MCAO大鼠和氧糖剥夺(OGD)条件下的SH-SY5Y细胞中均抑制NLRP3炎性小体的表达。而且,由NLRP3炎性小体介导且在MCAO大鼠中升高的包括白细胞介素-1β(IL-1β)和IL-18在内的炎性细胞因子水平可被QNDP降低,这表明QNDP可通过NLRP3炎性小体介导的机制保护神经元免受炎症侵害。核因子-κB(NF-κB)也参与了QNDP的抗炎作用。总之,QNDP通过抑制NLRP3炎性小体信号通路对脑缺血具有神经保护作用,是未来治疗缺血性中风的潜在候选药物。