地塞米松对利多卡因神经毒性的保护作用

Protective effects of dexamethasone on lidocaine-induced neurotoxicity in mouse neuroblastoma cells

目的观察地塞米松(Dex)对利多卡因(Lido)诱导小鼠神经母细胞瘤细胞株(N2a)毒性的影响。方法用0、100、250、500、1000和1500μmol/LLido孵化N2a细胞9h后,将细胞分为对照(Con)组、Lido组、Dex组和Dex+Lido组,观察细胞形态学变化,并检测细胞凋亡率和细胞Akt磷酸化水平。结果 (1)与0μmol/LLido比较,100、250和500μmol/LLido未引起明显细胞形态学变化,而1000和1500μmol/LLido引起显著细胞损伤;100和250μmol/LLido未引起明显的细胞凋亡增加,而500、1000、1500μmol/LLido分别引起轻度、中度和重度细胞凋亡(P<0.01)。(2)Dex+Lido组核固缩率显著低于Lido组(P<0.01)。(3)Dex+Lido组N2a细胞中Akt磷酸化水平显著高于Lido组(P<0.01)。结论 Lido呈浓度依赖性地诱导N2a细胞损伤,Dex预处理显著减轻Lido所致的细胞损伤,其保护机制与抑制Lido诱导的Akt脱磷酸化有关。

Objective To investigate the effects of dexamethasone（Dex） on the neurotoxicity of lidocaine（Lido） in mouse neuroblastoma N2a cells. Methods After N2a cells were incubated with Lido 0,100,250,500, 1 000 or 1 500 μmol/L for 9 h, the cells were divided into groups of control （Con）,Lido,Dex,and Dex＋ Lido. Apoptosis and phosphorylation level of Akt were evaluated. Results （1） Compared with Lido 0 μmol/L, Lido 100,250, and 500 /,mol/L did not induce significant cellular morphology alteration, however, Lido 1 000 and 1 500 mmol/L induced a significant cellular injury. Lido 100 and 250 μmol/L did not cause significantly increased apoptosis, however, Lido 500, 1 000, and 1 500μmol/L caused mild, moderate, and severe apoptosis, respectively（P〈0.01）. （2） Dex pretreatment attenuated Lido-induced apoptosis significanlly （P 〈 0.01 ）. （3） Dex pretreatment inhibited Lido induced dephosphorylation of Akt（P〈0.01）. Conclusion Lido causes neurotoxicity in N2a ceils dose-dependently. Dex pretreatment attenuates the neuron injury of Lido. The neuroproteetion of Dex is related to the inhibition of Lido induced dephosphorylation of Akt.