摘要
目的:观察脊髓p38丝裂原活化蛋白激酶(p38 MAPK)的激活对神经病理性疼痛大鼠热痛觉过敏的影响,探讨神经痛的机制。方法:40只雄性SD大鼠,建立坐骨神经结扎性损伤(CCI)疼痛模型,随机分成五组,对照组、SB 0.1μg组、SB0.5μg组、SB2.5μg组和SB5μg组,(n=8),CCI后7 d,鞘内注射5%二甲基亚砜或不同剂量的p38 MAPK抑制剂SB203580(0.1μg、0.5μg、2.5μg、5μg)10μL,在给药前和给药后0.5 h、3 h、6 h、12 h、24 h,用热辐射刺激仪测定大鼠术侧后爪热缩足反射潜伏期(TWL)。另24只大鼠随机分为假手术组、CCI组、溶媒对照组和SB203580组(n=6),分别于假手术后7d、CCI后7 d、CCI后7 d鞘内注射5%二甲基亚砜后第6 h或SB203580 5μg后第6 h取材脊髓,用免疫组织化学方法观察脊髓背角磷酸化p38 MAPK表达的变化。结果:鞘内注射SB203580剂量依赖性地延长了TWL(P<0.05或P<0.01),SB203580同时抑制脊髓背角磷酸化p38 MAPK的表达。结论:脊髓p38 MAPK的激活参与了CCI后神经痛的形成,抑制其活性可有效减轻神经痛大鼠的热痛觉过敏反应。
Objective： To investigate the effect of a specific p38MAPK inhibitor SB203580 on thermal hyperalgesia of neuropathic pain rats.Methods： Male SD rats were used in this study.The neuropathic pain model was established by Chronic constrictive injury to sciatic nerve.40 rats were randomly divided into 5 groups（n=8）： control group and 4 SBgroups（SB203580 0.1 μg,0.5 μg,2.5 μg and 5 μg were given respectively）.Thermal withdrawal latency（TWL） was measured before and at 0.5 h,3 h,6 h,12 h and 24 h after intrathecal SB203580 ingection.Another 24 rats were randomly divided into 4 groups（n=6）：（1） sham operation group;（2） CCI group;（3） DMSO group;（4） SBgroup.The rats were killed at 6h after DMSO or SB203580 administration for determination the p-p38MAPK expression in spinal by immuno-cytochemistry.Results： Intrathecal administration of SB203580 significantly lengthened TWL in a dose dependent manner and inhibited the CCI-induced increased in p-p38MAPK expression.Conclusion： the activation of p38MAPK in spical contributes to the development of neuropathic pain,and SB203580 can attenuate the thermal hyperalgesia of neuropathic pain induced by CCI.
出处
《长治医学院学报》
2010年第5期329-332,共4页
Journal of Changzhi Medical College
基金
和平医院科研发展基金资助项目(0806)
