褪黑素对吗啡导致的痛觉过敏及脊髓星形胶质细胞的作用研究  

Melatonin can prevent morphine induced hyperalgesia and spinal astrocytes activation in rats

作　　者：魏昕[1] 章蔚[1] 柴小青[1] 

机构地区：[1]安徽医科大学附属省立医院麻醉科,安徽合肥230001

出　　处：《安徽医药》2014年第1期15-19,共5页Anhui Medical and Pharmaceutical Journal

摘　　要：目的观察褪黑素(Melatonin,MT)对吗啡停药后的痛觉过敏及脊髓胶质细胞活化的影响。方法 62只SD大鼠,随机分为5组,分别为吗啡组(n=10),MT复合吗啡组[分三个剂量组(n=14×3)]以及生理盐水对照组(n=10)。吗啡10 mg·kg-1每日8:00 am以及6:00 pm皮下注射,连续7 d,诱导吗啡耐受及痛敏模型;MT于每日5:00 pm,分上述25、50、100 mg·kg-1三个剂量组灌胃给药。分别于用药前,用药后每日10:00—12:00am以及停药后第1、2天同一时间测定大鼠甩尾潜伏期。停药后第1、2天取脊髓行GFAP免疫组化染色和Western blot法GFAP测定。于停药后第1天取腰段脊髓,放免法测定cAMP和PKC水平。结果吗啡药后第1、2天,甩尾潜伏期显著缩短(与基础值比较,P<0.05),表现为痛觉过敏现象。MT 50、100mg·kg-1与吗啡联合用药组,停药后第1、2天无痛觉过敏现象(P>0.05)。吗啡停药后脊髓后角GFAP蛋白表达增强,用药第7天,停药后第1、2天GFAP表达均显著增加(P<0.05),cAMP和PKC水平明显增高。MT三个浓度组MT 25、50、100 mg·kg-1可显著抑制吗啡导致的上述GFAP高表达现象。MT在100 mg·kg-1剂量组时,可抑制吗啡导致cAMP水平增高,在50、100 mg·kg-1剂量组时,可抑制吗啡导致PKC水平增高。结论 MT在一定浓度和剂量范围内,显著预防吗啡慢性给药后急性停药导致的痛觉过敏,机制可能与抑制脊髓星形胶质细胞活化和PKC活性有关。Objective To investigate the effect of mdatonin on tolerance, hyperalgesia and reactive gliosis induced by morphine in rats. Methods The study examined the effect of melstonin on morphine-induced hyperalgesia using tail flick test. hnmunohistochemistt7 and western blot was performed to detect the expression of glial fibrillat7 acidic protein （GFAP） indicative of spinal glial activity. Radioim- munoasssy was employed to measure protein kinase C （PKC） activity and cAMP levels in spinal cords. Results When co-adminis- tered intragastrically （i. g. ） with morphine,melstonin in doses of 50 or 100 mg ~ kg ~ significantly prevented hyperalgesia after termi- nation of morphine, hnmunohistochemistry and western blot with glial fibrillat3, acidic protein （GFAP） revealed that melstonin signifi- cantly decreased morphine-induced overexpression of GFAP in spinal cord （P 〈 0.05）. By measuring protein kinase C （PKC） activity and cAMP levels,the upregulsted PKC activity and cAMP levels induced by morphine were significantly inhibited by melstonin. Con- dusions Melstonin can prevent morphine withdrawal induced hyperalgesia and glial reactivity. This effect of melstonin after morphine administration maybe mediated by inhibiting PKC activity and cAMP upregulstion.

关 键 词：褪黑素 吗啡 痛觉过敏 胶质纤维酸性蛋白 蛋白激酶C 

分 类 号：R965[医药卫生—药理学]