Chen Meng-Ling, Bao Feng, Zhang Yu-Qiu, Zhao Zhi-Qi
School of Bioscience and Food Engineering, Changshu Institute of Technology, Changshu 215500, China.
Sheng Li Xue Bao. 2012 Aug 25;64(4):365-71.
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.
先前的研究表明水通道蛋白4（AQP4）缺乏会减弱阿片类物质身体依赖性。然而，其潜在机制仍不清楚。在本研究中，利用蛋白质印迹分析，在AQP4基因敲除小鼠中研究了AQP4缺乏对脊髓中已知与脊髓神经元致敏和阿片类物质依赖性有关的三种因子，即蛋白激酶C（PKC）α、PKCγ和c-Fos表达的影响。观察到与野生型相比，AQP4缺乏使重复给予吗啡后纳洛酮诱发的戒断跳跃评分降低（P < 0.001）。同时，AQP4基因敲除小鼠脊髓中PKCα和c-Fos的蛋白水平显著高于野生型小鼠；而在戒断期间，AQP4基因敲除使PKCγ的表达显著降低（P < 0.01）。这些数据表明，AQP4缺乏减弱的吗啡戒断反应可能部分归因于PKCα、PKCγ或c-Fos脊髓表达的变化。
