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水通道蛋白4敲除对吗啡戒断小鼠脊髓PKCα、PKCγ及c-Fos的影响

陈梦玲, 鲍峰, 张玉秋, 赵志奇

常熟理工学院生物与食品工程学院，常熟 215500； 复旦大学神经生物学研究所，上海 210032

摘要

水通道蛋白4 (aquaporin 4, AQP4)基因敲除小鼠的阿片类躯体依赖症状减轻，但其具体机制至今仍不清楚。本实验通过免疫印迹法观察了与神经元敏化、阿片依赖密切相关的三个重要因子——蛋白激酶C (protein kinase C, PKC)亚型α、γ以及c-Fos在AQP4基因敲除小鼠脊髓中的表达变化。结果显示，小鼠反复慢性给予吗啡后，用纳洛酮诱导其产生急性戒断反应，AQP4基因敲除小鼠的蹦跳次数较野生型显著减少(P < 0.001)，且其脊髓中PKCα及c-Fos的蛋白水平显著高于野生型，而PKCγ的蛋白表达显著低于野生型(P < 0.01)。由此提示，AQP4基因敲除小鼠的吗啡戒断反应减弱，可能与脊髓中PKCα、PKCγ及c-Fos的蛋白表达与野生型之间存在差异有关。

关键词： 水通道蛋白4; c-Fos蛋白; 小鼠; 吗啡戒断; 脊髓; 蛋白激酶C

分类号：Q426

Effects of aquaporin 4 deficiency on the expression of spinal PKCα, PKCγ and c-Fos in naloxone-precipitated morphine withdrawal mice

CHEN Meng-Ling, BAO Feng, ZHANG Yu-Qiu, ZHAO Zhi-Qi

School of Bioscience and Food Engineering, Changshu Institute of Technology, Changshu 215500, China； Institute of Neurobiology, Fudan University, Shanghai 200032, China

Abstract

The previous study indicated that aquaporin 4 (AQP4) deficiency attenuated opioid physical dependence. However, the underlying mechanism remains unknown. In the present study, the effects of AQP4 deficiency on the expression of three factors, protein kinase C (PKC) α, PKCγ and c-Fos in the spinal cord, which are known to be concerned with spinal neuronal sensitization and opiate dependence, were investigated in AQP4 knockout mice using Western blotting analysis. It was observed that AQP4 deficiency reduced the score of naloxone-precipitated abstinent jumping after repeated morphine administration compared with wild-type (P < 0.001). Meanwhile, the protein levels of PKCα and c-Fos in the spinal cord of AQP4 knockout mice were significantly higher than those in the wild-type mice; while the expression of PKCγ was decreased remarkably by AQP4 knockout during the withdrawal (P < 0.01). These data suggest that AQP4 deficiency-attenuated morphine withdrawal responses may be partially attributed to the changes in the spinal expression of PKCα, PKCγ or c-Fos.

Key words: aquaporin 4; c-Fos; mice; morphine withdrawal; spinal cord; protein kinase C

收稿日期：2011-12-26　　录用日期：2012-03-29

通讯作者：陈梦玲,赵志奇　　E-mail: zqzhao@fudan.edu.cn, cml1003@gmail.com

引用本文：

陈梦玲, 鲍峰, 张玉秋, 赵志奇. 水通道蛋白4敲除对吗啡戒断小鼠脊髓PKCα、PKCγ及c-Fos的影响[J]. 生理学报 2012; 64 (4): 365-371.

CHEN Meng-Ling, BAO Feng, ZHANG Yu-Qiu, ZHAO Zhi-Qi. Effects of aquaporin 4 deficiency on the expression of spinal PKCα, PKCγ and c-Fos in naloxone-precipitated morphine withdrawal mice. Acta Physiol Sin 2012; 64 (4): 365-371 (in Chinese with English abstract).