Chen Chao, Zhu Feiyu, Liu Feifan, Yao Yufeng, Ma Zhihong, Luo Shanhong
Department of Anesthesia, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou 313000, Zhejiang, China.
Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou 313000, Zhejiang, China.
Iran J Public Health. 2023 Apr;52(4):756-765. doi: 10.18502/ijph.v52i4.12446.
Local anesthetic lidocaine is one of the most common pain therapies, but high concentration of lidocaine induced neurotoxicity and its mechanism is unclear. Exosomal microRNAs (miRNAs) is implicated in neuronal diseases, but its role in lidocaine induced neurotoxicity remains to be elucidated.
All the experiments were performed at Huzhou Key Laboratory of Molecular Medicine, Huzhou City, Jiangsu Province, China in 2022. Lidocaine was used to induce apoptosis of SH-SY5Y cells. Exosomes isolated from bone marrow mesenchymal stem cells (BMSC-exos) were used to co-treat SH-SY5Y cells with lidocaine. Cell apoptosis was measured using a flow cytometer. PKH-67 Dye was used for exosome uptake assay. miR-21-5p mimics/inhibitors, or negative controls were transfected with Lipo2000 to study its effect on lid-induced injury. Interactions between miR-21-5p and PDCD4 was analyzed by luciferase reporter assay.
Administration of BMSC-exo protected SH-SY5Y cells against lidocaine induced apoptosis. Suppressing miR-21-5p dramatically enhanced PDCD4, but miR-21-5p overexpression sharply down-regulated PDCD4. Mechanism study showed that miR-21-5p bound to 3'-UTR of PDCD4 to inhibit it. Suppressing miR-21-5p reversed the effect of BMSC-exo on Lid-induced injury. Results also indicate that miR-21-5p regulated lidocaine-induced injury through targeting PDCD4.
BMSC-exos protected SH-SY5Y cells against lidocaine induced apoptosis through miR-21-5p by targeting PDCD4, which may develop new strategy in the management of lidocaine-induced neurotoxicity.
局部麻醉药利多卡因是最常见的疼痛治疗药物之一，但高浓度利多卡因会诱发神经毒性，其机制尚不清楚。外泌体微小RNA（miRNA）与神经元疾病有关，但其在利多卡因诱导的神经毒性中的作用仍有待阐明。
所有实验于2022年在中国江苏省湖州市分子医学重点实验室进行。使用利多卡因诱导SH-SY5Y细胞凋亡。从骨髓间充质干细胞分离的外泌体（BMSC-exos）用于与利多卡因共同处理SH-SY5Y细胞。使用流式细胞仪测量细胞凋亡。PKH-67染料用于外泌体摄取测定。用Lipo2000转染miR-21-5p模拟物/抑制剂或阴性对照，以研究其对利多卡因诱导损伤的影响。通过荧光素酶报告基因测定分析miR-21-5p与PDCD4之间的相互作用。
给予BMSC-exo可保护SH-SY5Y细胞免受利多卡因诱导的凋亡。抑制miR-21-5p可显著增强PDCD4，但miR-21-5p过表达则会急剧下调PDCD4。机制研究表明，miR-21-5p与PDCD4的3'-UTR结合以抑制它。抑制miR-21-5p可逆转BMSC-exo对利多卡因诱导损伤的作用。结果还表明，miR-21-5p通过靶向PDCD4调节利多卡因诱导的损伤。
BMSC-exos通过靶向PDCD4的miR-21-5p保护SH-SY5Y细胞免受利多卡因诱导的凋亡，这可能为利多卡因诱导的神经毒性管理开发新策略。
