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Human Bone Marrow Mesenchymal Stem Cells-Derived Exosomal miRNA-21-5p Inhibits Lidocaine-Induced Apoptosis in SH-SY5Y
Chao Chen1, Feiyu Zhu1, Feifan Liu1
1Department of Anesthesia, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou 313000, Zhejiang, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Bone marrow mesenchymal stem cell exosomes protect against lidocaine neurotoxicity by regulating miR-21-5p and PDCD4. This finding offers a potential new strategy for managing lidocaine-induced nerve damage.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- High concentrations of the local anesthetic lidocaine can cause neurotoxicity, with unclear underlying mechanisms.
- Exosomal microRNAs (miRNAs) are implicated in neuronal diseases, but their role in lidocaine-induced neurotoxicity is not well understood.
Purpose of the Study:
- To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) against lidocaine-induced neurotoxicity.
- To elucidate the role of miR-21-5p and its target PDCD4 in this process.
Main Methods:
- SH-SY5Y cells were treated with lidocaine to induce apoptosis.
- BMSC-exos were used to co-treat cells with lidocaine.
- Cell apoptosis was assessed via flow cytometry.
- miR-21-5p mimics/inhibitors were transfected to study its effect on lidocaine-induced injury.
- Luciferase reporter assays were performed to analyze the interaction between miR-21-5p and PDCD4.
Main Results:
- BMSC-exos administration protected SH-SY5Y cells from lidocaine-induced apoptosis.
- miR-21-5p was found to target PDCD4, down-regulating its expression.
- Inhibition of miR-21-5p enhanced PDCD4 levels and reversed the protective effect of BMSC-exos.
Conclusions:
- BMSC-exos exert neuroprotective effects against lidocaine-induced apoptosis via the miR-21-5p/PDCD4 pathway.
- This mechanism presents a potential therapeutic strategy for managing lidocaine neurotoxicity.

