| 引用本文: | 王文元,蔡放,毛慧,胡双飞.LiCl对七氟醚引起的神经细胞凋亡的缓解作用[J].中国现代应用药学,2015,32(5):524-529. |
| WANG Wenyuan,CAI Fang,MAO Hui,HU Shuangfei.Attenuate Effect of LiCl on Neuronal Apoptosis Induced by Sevoflurane[J].Chin J Mod Appl Pharm(中国现代应用药学),2015,32(5):524-529. |
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| 摘要: |
| 目的 研究氯化锂(LiCl)对中枢神经系统发育期七氟醚神经毒性的影响，以及β-arrestin2/AKT信号通路在其中所起的作用。方法 对离体培养7 d的海马神经细胞及出生后7 d的Sprague-Dawley幼鼠进行七氟醚处理(3%，6 h)，制备七氟醚神经毒性模型。离体实验中给予LiCl或LiCl+β-arrestin2 siRNA转染处理后，应用流式细胞仪、MTT及Hoechst染色检测细胞凋亡；应用免疫印迹检测total AKT、Phospho-AKT、total GSK3β、Phospho-GSK3β、Bax及Bcl-2的蛋白表达水平；应用条件恐惧实验及Morris水迷宫检测实验动物的情绪及空间学习记忆功能变化。结果 七氟醚处理(3%，6 h)使海马神经细胞凋亡增加，应用LiCl则可明显缓解七氟醚神经毒性。七氟醚处理可降低Phospho-AKT及Bcl-2的蛋白表达，增加Phospho-GSK3β及Bax的蛋白表达；LiCl可增加Phospho-AKT及Bcl-2表达，降低Phospho-GSK3β及Bax表达水平。LiCl的神经保护作用可被转染β-arrestin2 siRNA、SH-5或LY294002所逆转。LiCl明显缓解了中枢神经系统发育期七氟醚处理引起的情绪及空间学习记忆功能异常。结论 LiCl可缓解中枢神经系统七氟醚神经毒性，其机制可能与β-arrestin2依赖的AKT/GSK3β信号通路有关。 |
| 关键词: 七氟醚 氯化锂 细胞凋亡 β-arrestin2 AKT/GSK3β 神经发育 |
| DOI： |
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| 基金项目:国家自然科学基金项目(81302858) |
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| Attenuate Effect of LiCl on Neuronal Apoptosis Induced by Sevoflurane |
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WANG Wenyuan, CAI Fang, MAO Hui, HU Shuangfei
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Zhejiang Provincial People’s Hospital, Hangzhou 310014, China
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| Abstract: |
| OBJECTIVE To examine the effects of LiCl on developmental sevoflurane-induced neuronal apoptosis and the role of β-arrestin2/AKT signaling pathway. METHODS The developmental sevoflurane neurotoxicity model was established by exposure of primary hippocampal neurons (7 days in vitro) and Sprague-Dawley rat pups (7 postnatal days) with sevoflurane (3%, 6 h). The cells were treated with LiCl or combined with β-arrestin2 siRNA transfection. The neuronal apoptosis was analyzed by flow cytometry (FCM), MTT and Hoechst-staining. The relative expressions of total AKT, Phospho-AKT, total GSK3β, Phospho-GSK3β, Bax and Bcl-2 were determined by western blot. The emotional and spatial cognitive functions were examined by fear conditioning and Morris water maze. RESULTS Sevoflurane exposure (3%, 6 h) significantly enhanced the neuronal apoptosis, which could be ameliorated by LiCl. Sevoflurane decreased the expressions of Phospho-AKT and Bcl-2, but increased Phospho-GSK3β and Bax. LiCl significantly elevated the expressions of Phospho-AKT and Bcl-2, but decreased Phospho-GSK3β and Bax. The neuronal protective role of LiCl was abolished by β-arrestin2 siRNA transfection, SH-5 or LY294002. In addition, LiCl significantly improved the emotional and spatial cognitive disorders induced by postnatal sevoflurane exposure. CONCLUSION Application of LiCl can prevent developmental sevoflurane neurotoxicity, and the β-arrestin2-dependent AKT/GSK3β signaling pathway may be involved in this process. |
| Key words: sevoflurane LiCl cell apoptosis β-arrestin2 AKT/GSK3β neuronal development |
