Author:
Xu Weicai,Li Xiaojun,Chen Long,Luo Xiaopan,Shen Sheliang,Wang Jing
Abstract
Abstract
Background
Ropivacaine is commonly applied for local anesthesia and may cause neurotoxicity. Dexmedetomidine (DEX) exhibits neuroprotective effects on multiple neurological disorders. This study investigated the mechanism of DEX pretreatment in ropivacaine-induced neurotoxicity.
Methods
Mouse hippocampal neuronal cells (HT22) and human neuroblastoma cells (SH-SY5Y) were treated with 0.5 mM, 1 mM, 2.5 mM, and 5 mM ropivacaine. Then the cells were pretreated with different concentrations of DEX (0.01 μM, 0.1 μM, 1 μM, 10 μM, and 100 μM) before ropivacaine treatment. Proliferative activity of cells, lactate dehydrogenase (LDH) release, and apoptosis rate were measured using CCK-8 assay, LDH detection kit, and flow cytometry, respectively. miR-10b-5p and BDNF expressions were determined using RT-qPCR or Western blot. The binding of miR-10b-5p and BDNF was validated using dual-luciferase assay. Functional rescue experiments were conducted to verify the role of miR-10b-5p and BDNF in the protective mechanism of DEX on ropivacaine-induced neurotoxicity.
Results
Treatment of HT22 or SH-SY5Y cells with ropivacaine led to the increased miR-10b-5p expression (about 1.7 times), decreased BDNF expression (about 2.2 times), reduced cell viability (about 2.5 times), elevated intracellular LDH level (about 2.0–2.5 times), and enhanced apoptosis rate (about 3.0–4.0 times). DEX pretreatment relieved ropivacaine-induced neurotoxicity, as evidenced by enhanced cell viability (about 1.7–2.0 times), reduced LDH release (about 1.7–1.8 times), and suppressed apoptosis rate (about 1.8–1.9 times). DEX pretreatment repressed miR-10b-5p expression (about 2.5 times). miR-10b-5p targeted BDNF. miR-10b-5p overexpression or BDNF silencing reversed the protective effect of DEX pretreatment on ropivacaine-induced neurotoxicity, manifested as reduced cell viability (about 1.3–1.6 times), increased intracellular LDH level (about 1.4–1.7 times), and elevated apoptosis rate (about 1.4–1.6 times).
Conclusions
DEX pretreatment elevated BDNF expression by reducing miR-10b-5p expression, thereby alleviating ropivacaine-induced neurotoxicity.
Publisher
Springer Science and Business Media LLC
Subject
Anesthesiology and Pain Medicine
Reference52 articles.
1. Xu P, Zhang S, Tan L, Wang L, Yang Z, Li J. Local Anesthetic Ropivacaine Exhibits Therapeutic Effects in Cancers. Front Oncol. 2022;12: 836882. https://doi.org/10.3389/fonc.2022.836882.
2. Li M, Wan L, Mei W, Tian Y. Update on the clinical utility and practical use of ropivacaine in Chinese patients. Drug Des Devel Ther. 2014;8:1269–76. https://doi.org/10.2147/DDDT.S57258.
3. Wen X, Liang H, Li H, Ou W, Wang HB, Liu H, et al. In vitro neurotoxicity by ropivacaine is reduced by silencing Cav3.3 T-type calcium subunits in neonatal rat sensory neurons. Artif Cells Nanomed Biotechnol. 2018;46:1617–24.
4. Sun Z, Liu H, Guo Q, Xu X, Zhang Z, Wang N. In vivo and in vitro evidence of the neurotoxic effects of ropivacaine: the role of the Akt signaling pathway. Mol Med Rep. 2012;6:1455–9. https://doi.org/10.3892/mmr.2012.1115.
5. Sun ZH, Xu XP, Song ZB, Zhang Z, Wang N, Guo QL. Repeated intrathecal administration of ropivacaine causes neurotoxicity in rats. Anaesth Intensive Care. 2012;40:825–31. https://doi.org/10.1177/0310057X1204000427.
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