ATPase Inhibitory Factor 1 Is Critical for Regulating Sevoflurane-Induced Microglial Inflammatory Responses and Caspase-3 Activation.
ATPase Inhibitory Factor 1 Is Critical for Regulating Sevoflurane-Induced Microglial Inflammatory Responses and Caspase-3 Activation.
复制标题
ATPase 抑制因子 1 对于调节七氟烷诱导的小胶质细胞炎症反应和 Caspase-3 激活至关重要
DOI：
10.3389/fncel.2021.770666
复制
发表时间：
2021
影响因子：
5.3
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Xu Y;Gao G;Sun X;Liu Q;Li C
术后谵妄（POD）是全身麻醉手术后最重要的并发症之一，全身麻醉药物的神经毒性是其高危因素。然而，其机制仍不清楚，这也阻碍了POD的有效治疗。在此，我们证实临床浓度的全身麻醉药七氟烷可通过上调小胶质细胞中 ATP 酶抑制因子 1 (ATPIF1) 的表达来增加炎症因子的表达并激活 caspase-3。 ATPIF1 的上调减少了 ATP 的合成，ATP 是小胶质细胞分泌的重要信号分子。细胞外补充 ATP 可减弱七氟烷或 ATPIF1 过度表达引起的小胶质细胞炎症反应和 caspase-3 激活。此外，小胶质细胞炎症反应进一步上调 ATPIF1 表达，形成正反馈循环。动物实验进一步表明，腹腔注射ATP可显着减轻七氟烷麻醉引起的小鼠POD相关焦虑行为和记忆损伤。这项研究揭示了 ATPIF1（一种调节 ATP 合成的重要蛋白质）介导小胶质细胞中七氟醚诱导的神经毒性。补充 ATP 可能是缓解七氟烷诱导的 POD 的潜在临床治疗方法。
Postoperative delirium (POD) is one of the most important complications after surgery with general anesthesia, for which the neurotoxicity of general anesthetics is a high-risk factor. However, the mechanism remains largely unknown, which also hinders the effective treatment of POD. Here, we confirmed that a clinical concentration of the general anesthetic sevoflurane increased the expression of inflammatory factors and activated the caspase-3 by upregulating ATPase inhibitory factor 1 (ATPIF1) expression in microglia. Upregulation of ATPIF1 decreased the synthesis of ATP which is an important signaling molecule secreted by microglia. Extracellular supplementation with ATP attenuated the microglial inflammatory response and caspase-3 activation caused by sevoflurane or overexpression of ATPIF1. Additionally, the microglial inflammatory response further upregulated ATPIF1 expression, resulting in a positive feedback loop. Animal experiments further indicated that intraperitoneal injection of ATP significantly alleviated sevoflurane anesthesia-induced POD-related anxiety behavior and memory damage in mice. This study reveals that ATPIF1, an important protein regulating ATP synthesis, mediates sevoflurane-induced neurotoxicity in microglia. ATP supplementation may be a potential clinical treatment to alleviate sevoflurane-induced POD.
登录
查看更多内容
影响因子：
2.1
作者：
Kinjo S;Lim E;Magsaysay MV;Sands LP;Leung JM;Perioperative Medicine Research Group
通讯作者：
Perioperative Medicine Research Group
影响因子：
5.3
作者：
Jha MK;Morrison BM
通讯作者：
Morrison BM
影响因子：
4.8
作者：
Clarke, Rachael M.;Lyons, Anthony;Lynch, Marina A.
通讯作者：
Lynch, Marina A.
影响因子：
5.4
作者：
Dong P;Zhang X;Zhao J;Li D;Li L;Yang B
通讯作者：
Yang B
影响因子：
9
作者：
Bras, Joao Paulo;Bravo, Joana;Almeida, Maria Ines
通讯作者：
Almeida, Maria Ines