Effects Of Dexmedetomidine On Highly Concentrated Lidocaine-induced Cytotoxicity In PC12 Cells

Objective: It has been known that highly concentrated lidocaine can induce neurotoxicity in vivo.The objective of this study was to construct a cytotoxicity model of highly concentrated lidocaine and observe epigenetic regulations of dexmedetomidine preconditioning on the cytotoxicity induced by highly concentrated lidocaine in vitro.Methods: Firstly it was to construct a cytotoxicity model of highly concentrated lidocaine in vitro and to observe the viability of the PC12 cells.The PC12 cells cultured in vitro were treated with dexmedetomidine and lidocaine combined.After 48 hours,the viability of PC12 cells was measured and the proliferation inhibition rate was calculated while the apoptosis level and the MAPK signaling pathway proteinexpression were detected.The miR-let-7b and its possible target protein COL3A1 were predicted by literatures and software and the relationship between them was verified.The binding of miR-let-7b to COL3A1-3'UTR was examined,in which the cell viability,cell proliferation level,apoptosis level,cell migration and invasive ability,cell cycle and apoptotic protein were measured under the condition of combined administration of lidocaine and dexmedetomidine.Results: Lidocaine 1m M can significantly reduce the PC12 cell viability.The PC12 cells treated by dexmedetomidine can significantly increase cell viability,reduce proliferation inhibiting rate,inhibitapoptosis level and decrease the protein level in MAPK signaling pathway.Dexmedetomidine,over-expression of miR-let-7b and silencing expression of COL3A1 can all increase cell viability,cell invasion and migration ability,decrease proliferation inhibition rate,inhibit apoptosis level,change cell cycle,up-regulate Bcl-2 expression and down-regulate the expression of Caspase-3.Conclusions: Dexmedetomidine preconditioning can reduce cytotoxicity induced by highly concentraed lidocaine through upregulating miR-let-7b and/or downregulating COL3A1 levels in PC12 cells,suggesting that miR-let-7b have therapeutic potential for neurotoxicity induced by highly concentrated lidocaine,and it is a simple,effective way to reduce cytotoxicity with dexmedetomidine preconditioning.