Liu Hai-Lin, Cao Jun-Li, Dai Pei-Jing, Zheng Guo-Long, Zeng Ying-Ming
Department of Anesthesiology, 1st Hospital of Huai'an, Affiliated Hospital of Nanjing Medical University, Huai'an 223300, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2007 Feb;23(1):5-8.
To explore effects of intrathecal injection of U0126 on morphine withdrawal response and the spinal Phospho-CREB expression in morphine-induced withdrawal rats.
All the rats were divided into 5 groups: control group, dependence group, withdrawal group, U0126 group (5 microg, it) and DMSO group. Morphine withdrawal score, touch evoked agitation scores(TEA score), immunohistochemical and Western-blotting technique were used to evaluate morphine withdrawal response and the expression of Phospho-CREB in the spinal cord.
Intrathecal injection of MEK inhibitor U0126 significantly alleviated morphine withdrawal symptoms. Morphine withdrawal scores in U0126 group (22.5 +/- 4.09) were significantly lower than that of withdrawal group (28.6 +/- 4.89, P < 0.05). TEA score of withdrawal group was 13.5 +/- 2.55, which was significantly higher than that of U0126 group (10.0 +/- 2.76, P < 0.05). Phospho-CREB positive neurons in the spinal dorsal horn of withdrawal group were 380 +/- 71, which is higher than that of U0126 group (293 +/- 47, P < 0.05). Compared with withdrawal group, level of Phospho-CREB protein detected by Western blot in spinal cord of U0126 group was significantly lower.
MEK inhibitors U0126 could suppress expression of Phospho-CREB in the spinal cord.
探讨鞘内注射U0126对吗啡成瘾大鼠戒断反应及脊髓磷酸化环磷腺苷反应元件结合蛋白（Phospho-CREB）表达的影响。
将大鼠分为5组：对照组、成瘾组、戒断组、U0126组（5微克，鞘内注射）和二甲基亚砜（DMSO）组。采用吗啡戒断评分、触诱发怒评分（TEA评分）、免疫组化和蛋白质印迹技术评估吗啡戒断反应及脊髓中Phospho-CREB的表达。
鞘内注射丝裂原活化蛋白激酶/细胞外信号调节激酶（MEK）抑制剂U0126可显著减轻吗啡戒断症状。U0126组的吗啡戒断评分（22.5±4.09）显著低于戒断组（28.6±4.89，P<0.05）。戒断组的TEA评分为13.5±2.55，显著高于U0126组（10.0±2.76，P<0.05）。戒断组脊髓背角Phospho-CREB阳性神经元为380±71，高于U0126组（293±47，P<0.05）。与戒断组相比，U0126组脊髓中通过蛋白质印迹法检测到的Phospho-CREB蛋白水平显著降低。
MEK抑制剂U0126可抑制脊髓中Phospho-CREB的表达。
