Honokiol-Mediated Mitophagy Ameliorates Postoperative Cognitive Impairment Induced by Surgery/Sevoflurane via Inhibiting the Activation of NLRP3 Inflammasome in the Hippocampus
Honokiol-Mediated Mitophagy Ameliorates Postoperative Cognitive Impairment Induced by Surgery/Sevoflurane via Inhibiting the Activation of NLRP3 Inflammasome in the Hippocampus
复制标题
和厚朴酚介导的线粒体自噬通过抑制海马 NLRP3 炎症小体的激活改善手术/七氟烷引起的术后认知障碍
DOI：
10.1155/2019/8639618
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发表时间：
2019-01-01
影响因子：
--
通讯作者：
Xia, Zhong-Yuan
中科院分区：
文献类型：
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作者：
Ye, Ji-Shi;Chen, Lei;Xia, Zhong-Yuan
术后认知功能障碍的潜在机制仍不清楚。NLRP3炎性小体的激活已被报道参与神经退行性疾病，包括术后认知改变，并与线粒体ROS和线粒体自噬密切相关。本木酚（HNK）具有多种有机保护作用。本研究旨在观察HNK在手术/麻醉小鼠术后认知改变中的神经保护作用，探讨HNK在调节线粒体自噬中的作用及其与NLRP3炎性体激活的关系。方法将小鼠分为对照组、手术组、手术+HNK组、手术+HNK+3-甲基腺嘌呤（3-MA）组。收集海马组织样本，用于促炎细胞因子、线粒体ROS和丙二醛（MDA）测定。采用Western blot、免疫组织化学、透射电镜观察细胞自噬过程及NLRP3炎性体的活化。结果HNK治疗明显恢复了术后衰退，术后/七氟醚治疗后LC3-II、Beclin-1、Parkin、PINK1蛋白水平表达增强，这是自噬标志物和有丝分裂标志物。此外，HNK减轻了线粒体结构损伤，减少了与NLRP3炎性小体激活密切相关的mtROS和MDA的生成。檀香醇介导的线粒体自噬抑制海马NLRP3炎性体的激活和神经炎症。使用自噬抑制剂3-MA，消除HNK对线粒体自噬和NLRP3炎性体活化的神经保护作用。结论hnk介导的线粒体自噬可改善手术/七氟醚所致的术后认知功能障碍。这种神经保护作用可能与抑制NLRP3炎性体的激活和抑制海马的炎症反应有关。
Background The potential mechanism of postoperative cognitive impairment is still largely unclear. The activation of NLRP3 inflammasome had been reported to be involved in neurodegenerative diseases, including postoperative cognitive change, and is closely related to mitochondrial ROS and mitophagy. Honokiol (HNK) owns multiple organic protective effects. This study is aimed at observing the neuroprotective effect of HNK in postoperative cognitive change and examining the role of HNK in the regulation of mitophagy and the relationship between these effects and NLRP3 inflammasome activation in mice induced by surgery/anesthesia. Methods In this study, mice were divided into several groups: control group, surgery group, surgery+HNK group, and surgery+HNK+3-methyladenine (3-MA) group. Hippocampal tissue samples were harvested and used for proinflammatory cytokines, mitochondrial ROS, and malondialdehyde (MDA) assay. The process of mitophagy and the activation of NLRP3 inflammasome were observed by Western blot, immunohistochemistry, and transmission electron microscopy. Results The results showed that HNK treatment obviously recovered the postoperative decline and enhanced the expressions of LC3-II, Beclin-1, Parkin, and PINK1 at protein levels after surgery/sevoflurane treatment, which are both an autophagy marker and a mitophagy marker. In addition, HNK attenuated mitochondrial structure damage and reduced mtROS and MDA generation, which are closely associated with NLRP3 inflammasome activation. Honokiol-mediated mitophagy inhibited the activation of NLRP3 inflammasome and neuroinflammation in the hippocampus. Using 3-MA, an autophagy inhibitor, the neuroprotective effects of HNK on mitophagy and NLRP3 inflammasome activation were eliminated. Conclusion These results indicated that HNK-mediated mitophagy ameliorates postoperative cognitive impairment induced by surgery/sevoflurane. This neuroprotective effect may be involved in inhibiting the activation of NLRP3 inflammasome and suppressing inflammatory responses in the hippocampus.