FK866 alleviates cerebral pyroptosis and inflammation mediated by Drp1 in a rat cardiopulmonary resuscitation model.
FK866 alleviates cerebral pyroptosis and inflammation mediated by Drp1 in a rat cardiopulmonary resuscitation model.
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FK866 可减轻大鼠心肺复苏模型中由 Drp1 介导的脑焦亡和炎症。
DOI：
10.1016/j.intimp.2020.107032
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Menghua Chen
中科院分区：
文献类型：
--
作者：
Xinsen Zou;Lu Xie;Wenyan Wang;Gaoyang Zhao;Xinyue Tian;Menghua Chen
目的动力蛋白相关蛋白1（Drp 1）介导线粒体分裂并激活NLRP 3炎性小体。FK 866（NAMPT抑制剂）通过抑制线粒体功能障碍在缺血/再灌注损伤中发挥神经保护作用。我们探讨了FK 866对心脏骤停/心肺复苏（CA/CPR）大鼠模型中Drp 1介导的焦亡和炎症的影响。存活的大鼠用FK 866（NAMPT的选择性抑制剂）、Mdivi-1（Drp 1抑制剂）、FK 866 + Mdivi-1或溶剂处理，然后进行24 h再灌注。采用苏木精-伊红染色和免疫组化法检测NSE。我们进行免疫荧光染色以分析小胶质细胞或星形胶质细胞中NLRP 3和GSDMD的表达，并进行蛋白质印迹以确定NLRP 3、IL-1β、GSDMD、Drp 1和Mfn 2的表达。结果FK 866可明显减轻脑组织病理损伤，抑制小胶质细胞或星形胶质细胞NLRP 3的活化，下调NLRP 3、IL-1β、GSDMD、p-Drp 1蛋白的表达，上调Mfn 2并改善线粒体形态。结论我们的结果表明FK 866可以保护CA/后大鼠脑缺血再灌注损伤CPR通过抑制由Drp 1介导的焦亡和炎症。
ObjectivesDynamin-related protein 1 (Drp1) mediates mitochondrial fission and triggers NLRP3 inflammasome activation. FK866 (a NAMPT inhibitor) exerts a neuroprotective effect in ischemia/reperfusion injury through the suppression of mitochondrial dysfunction. We explored the effects of FK866 on pyroptosis and inflammation mediated by Drp1 in a cardiac arrest/cardiopulmonary resuscitation (CA/CPR) rat model.MethodsHealthy male Sprague-Dawley rats were subjected to 7 min CA bytrans-esophageal electrical stimulation followed by CPR. The surviving rats were treated with FK866 (a selective inhibitor of NAMPT), Mdivi-1 (Drp1 inhibitor), FK866 + Mdivi-1, or vehicle and then underwent 24 h reperfusion. Hematoxylin and eosin staining and immunohistochemistry (to detect NSE) were used to evaluate brain injury. We performed immunofluorescent staining to analyze NLRP3 and GSDMD expression in microglia or astrocytes and western blot to determine expression of NLRP3, IL-1β, GSDMD, Drp1, and Mfn2. Transmission electron microscopy was used to observe mitochondria.ResultsFK866 significantly decreased pathological damage to brain tissue, inhibited the activation of NLRP3 in microglia or astrocytes, downregulated the expression of NLRP3, IL-1β, GSDMD, p-Drp1 protein, upregulated Mfn2 and improve mitochondrial morphology.ConclusionsOur results demonstrated that FK866 protects the brain against ischemia-reperfusion injury in rats after CA/CPR by inhibiting pyroptosis and inflammation mediated by Drp1.
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在心脏骤停大鼠模型中，低温治疗通过抑制动力相关蛋白 1 激活和线粒体介导的细胞凋亡来减轻全脑再灌注引起的线粒体损伤
影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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