Liu Hai-Lin, Qian Yan-Ning, Li Xiang-Cheng
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. 2012 Jan;28(1):49-52.
To explore if induced nitric oxide in the spinal cord mediates withdrawal syndrome in morphine-dependent rats.
Male SD rats weighing 200-250 g were employed in the present study. To set up morphine dependence model, rats were subcutaneously injected with morphine (twice a day, for 5 d). The dose of morphine was 10 mg/kg in the first day and was increased by 10 mg/kg each day. On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal syndrome was precipitated by an injection of naloxone (4 mg/kg, ip). Inducible nitric oxide synthase (iNOS) inhibitors aminoguanidine (AG) was intrathecally injected 30 min before the administration of naloxone. All the rats were divided into four groups: control group, dependence group, withdrawal group, AG group. Morphine withdrawal score, touch evoked agitation scores (TEA scores), immunohistochemical and Western blot technique were used to evaluate morphine withdrawal response and the expression of iNOS in the spinal cord.
Intrathecal injection of iNOS inhibitors AG could alleviate morphine withdrawal symptoms. Morphine withdrawal scores and touch evoked agitation scores in AG group were significantly lower than that of withdrawal group (P < 0.05). iNOS positive neurons in dorsal horn of AG group were significantly lower than that of withdrawal group (P < 0.05). Level of iNOS protein in spinal cord of AG group was significantly lower than that of withdrawal group (P < 0.05).
Induced nitric oxide in the spinal cord may mediate withdrawal syndrome in morphine-dependent rats.
探讨脊髓中诱导型一氧化氮是否介导吗啡依赖大鼠的戒断综合征。
本研究采用体重200 - 250 g的雄性SD大鼠。为建立吗啡依赖模型，大鼠皮下注射吗啡（每日2次，共5天）。吗啡剂量首日为10 mg/kg，随后每日增加10 mg/kg。在第6天，注射吗啡（50 mg/kg）4小时后，腹腔注射纳洛酮（4 mg/kg）诱发吗啡戒断综合征。在给予纳洛酮前30分钟鞘内注射诱导型一氧化氮合酶（iNOS）抑制剂氨基胍（AG）。所有大鼠分为四组：对照组、依赖组、戒断组、AG组。采用吗啡戒断评分、触觉诱发激惹评分（TEA评分）、免疫组织化学和蛋白质印迹技术评估吗啡戒断反应及脊髓中iNOS的表达。
鞘内注射iNOS抑制剂AG可减轻吗啡戒断症状。AG组的吗啡戒断评分和触觉诱发激惹评分显著低于戒断组（P < 0.05）。AG组背角iNOS阳性神经元显著低于戒断组（P < 0.05）。AG组脊髓中iNOS蛋白水平显著低于戒断组（P < 0.05）。
脊髓中诱导型一氧化氮可能介导吗啡依赖大鼠的戒断综合征。
