Dexmedetomidine Protects SH-SY5Y Cells from Lidocaine-Induced Neurotoxicity via the AMPK/PGC-1 alpha Pathway

作者全名："Mu, Yang; Deng, Beiqiang; Yang, Zhiwen; li, Chunxiang; Xia, Juan"

作者地址："[Mu, Yang; Deng, Beiqiang] Chongqing Univ, Fuling Hosp, Dept Rehabil Med, Chongqing 408099, Peoples R China; [Yang, Zhiwen] Chongqing Univ, Fuling Hosp, Dept Emergency Med, Chongqing 408099, Peoples R China; [li, Chunxiang] Army Med Univ, Affiliated Hosp 1, Dept Anaesthesiol, Chongqing 400038, Peoples R China; [Xia, Juan] Chongqing Med Univ, Affiliated Hosp 2, Dept Anaesthesiol, Chongqing 400010, Peoples R China"

通信作者："Xia, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Anaesthesiol, Chongqing 400010, Peoples R China."

来源：JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000947805700001

JCR分区：Q4

影响因子：0.8

年份：2023

卷号：37

期号：1

开始页：543

结束页：553

文献类型：Article

关键词：lidocaine; dexmedetomidine (DEX); mitochondria; oxidative stress

摘要："Background: Nerve blocks that deliver lidocaine to specific neural structures are often considered for patients with neuropathic pain. However, there is evidence that lidocaine may induce neuronal cell apoptosis. Dexmedetomidine (DEX) can be used for nerve block and has neuroprotective effects. Therefore, we explored the effects of DEX (20 nM) + lidocaine (6 mM) on neuronal cell apoptosis and its underlying mechanism.Methods: In this study, we used SH-SY5Y cells, which were differentiated by all-trans retinoic acid (ATRA) treatment, were cultured in vitro and subsequently treated using lidocaine, lidocaine + DEX or DEX + compound C (CC, AMPK (adenosine monophosphate-activated protein kinase) inhibitor). Cell counting kit 8 (CCK-8) assay was employed to examine the viability of the cells. Apoptotic cell proportion was assessed by flow cytometry (FCM) and staining with Hoechst 33258, while the ROS (reactive oxygen species) and mitochondrial membrane potential ( increment psi m) were immunofluorescently evaluated. Apoptotic and mitochondrial biogenesis regulatory protein markers (cleaved caspase 3/9, Bax, Bcl-2 (B-cell lymphoma-2), p-AMPK, and PGC-1 alpha (peroxisome proliferator-activated receptor-gamma coactivator-1 alpha)) were analyzed by Western blotting.Results: Lidocaine treatment increased the apoptotic ratio and levels of cleaved caspase 3/9 and Bax while leading to dropped anti-apoptotic protein and Bcl-2 levels. After lidocaine treatment, there were an aggregation of ROS and a decline in increment psi m. Dex treatment reversed such alterations partially. Mechanistically, DEX increased the lidocaine-induced mitochondrial biogenesis protein, PGC-1 alpha, while DEX's effects were reversed by the AMPK inhibitor (CC) partially.Conclusions: Through the regulation of mitochondrial biogenesis, reduction of ROS and prevention of increment psi m loss, DEX attenuates the SH-SY5Y cell apoptosis elicited by lidocaine. DEX reduces lidocaine-induced neurotoxicity and provides a better way for the clinical use of lidocaine."

基金机构：National Natural Sci-ence Foundation of China [81870883]

基金资助正文：Funding This work was supported by the National Natural Sci-ence Foundation of China (81870883) .