State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China.
Biobank of Eye, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China.
Drug Des Devel Ther. 2021 Mar 2;15:927-936. doi: 10.2147/DDDT.S290002. eCollection 2021.
To assess the cellular and molecular effects of lidocaine on muscles/myoblasts.
Cultured myogenic precursor (C2C12) cells were treated with varying concentrations of lidocaine.
Cell viability of C2C12 cells was inhibited by lidocaine in a concentration-dependent manner, with concentrations ≥0.08%, producing a dramatic reduction in cell viability. These ≥0.08% concentrations of lidocaine arrested cell cycles of C2C12 cells in the G0/G1 phase. Moreover, lidocaine inhibited cell migration and myogenic processes in C2C12 cells at low concentrations. Results from QRT-PCR assays revealed that following treatment with lidocaine, Notch1, Notch2, Hes1, Csl and Dll4 all showed higher levels of expression, while no changes were observed in Mmal1, Hey1, Dll1 and Jag1.
This work provides the first description of the effects of lidocaine upon the regeneration of muscles and maintenance of satellite cells at the cellular and molecular levels. In specific, we found that the Dll4-Notch-Csl-Hes1 axis was up-regulated suggesting that the Notch signaling pathway was involved in producing these effects of lidocaine. These findings provide a new and important foundation for future investigations into the effects of drug therapies in muscle diseases.
评估利多卡因对肌肉/成肌细胞的细胞和分子作用。
用不同浓度的利多卡因处理培养的成肌前体细胞（C2C12）细胞。
利多卡因以浓度依赖的方式抑制 C2C12 细胞的细胞活力，浓度≥0.08%时，细胞活力显著降低。这些≥0.08%的利多卡因浓度使 C2C12 细胞的细胞周期停滞在 G0/G1 期。此外，利多卡因在低浓度时抑制 C2C12 细胞的迁移和成肌过程。QRT-PCR 检测结果显示，利多卡因处理后，Notch1、Notch2、Hes1、Csl 和 Dll4 的表达水平均升高，而 Mmal1、Hey1、Dll1 和 Jag1 无变化。
本研究首次描述了利多卡因在细胞和分子水平上对肌肉再生和卫星细胞维持的影响。具体来说，我们发现 Dll4-Notch-Csl-Hes1 轴被上调，提示 Notch 信号通路参与产生这些利多卡因的作用。这些发现为未来研究肌肉疾病药物治疗的作用提供了新的重要基础。
