摘要
目的在佐剂性关节炎大鼠模型基础上建立关节炎大鼠慢性吗啡耐受模型,观察兴奋性氨基酸载体1(EAAC1)在关节炎慢性吗啡耐受大鼠的脊髓背角表达的变化,探讨EAAC1在吗啡耐受形成机制中的作用。方法将36只健康雄性SD大鼠随机分为6组(n=6),行鞘内置管。其中4组制成佐剂性关节炎模型,分别经鞘内给予生理盐水(A组)、吗啡10μg(B组)、吗啡20μg(C组)、吗啡10μg加纳洛酮10μg(D组),另外两组非致炎大鼠分别经鞘内给予生理盐水(E组)、吗啡20μg(F组)。各组给药均为1日2次,连续7d。用VonFrey丝动态检测大鼠50%机械缩爪阈值,分别以免疫组化和Westernblot方法检测各组大鼠给予吗啡后脊髓背角EAAC1表达。结果B、C两组关节炎大鼠在鞘内给予吗啡后第7天形成较稳定的机械痛敏,标志关节炎大鼠慢性吗啡耐受模型建立成功,其脊髓背角EAAC1的表达下调。结论脊髓EAAC1可能参与炎性痛大鼠慢性吗啡耐受的形成机制。
【Objective】To construct the rat model of arthritis-chronic morphine tolerance which is based on the rat model of adjuvant-induced arthritis and to observe the change of expression of EAAC1 in spinal dorsal horn of rats with arthritis-chronic morphine tolerance in order to analyze the effect of EAAC1 on mechanism of the development of morphine tolerance.【Methods】Thirty-six healthy male SD rats were randomized into 6 groups （n=6） who were implanted intrathecal catheters. Amongst, the rats in four groups were made into model of adjuvant-induced arthritis and were intrathecally administered saline （group A）, morphine 10 μg （group B）, morphine 20 μg （group C）, morphine 10 μg and naloxone 10 μg （group D）, respectively. The rats in the remaining two groups without arthritis were intrathecally administered saline （group E）, morphine 20 μg （group F）, respectively. The drugs were adminis-tered twice daily for 7 days. Fifty percent Mechanical paw withdrawal threshold （PWT） of rats was examined to evalu-ate its behavior. Immunohistochemistry and Western blot were used to detect the expression of EAAC1 in spinal dorsal horn.【Results】Hyperalgesia was developed stably in the arthritis rats of group B and group C after administering morphine for 7 days, which indicated morphine tolerance formed. The expression of EAAC1 in spinal dorsal horn of rats with arthritis-chronic morphine tolerance was downregulated. 【Conclusion】Spinal EAAC1 may contribute to the mechanism of development of morphine tolerance in rats with inflammatory pain.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2010年第5期641-646,共6页
China Journal of Modern Medicine
基金
Supported by the Foundation of Tianjin Natural Science of China (No. 06YFJMJC08600)
the Technological Foundation of Tianjin Health Bureau (No:06KZ51)
