摘要
目的观察右美托咪定对芬太尼所致大鼠痛觉敏化的影响,并探索其可能机制。方法将130只雄性SD大鼠随机分为5组(n=26)。生理盐水组(NS组)大鼠皮下注射生理盐水1ml×5次;芬太尼组(即模型组,F组)大鼠皮下注射生理盐水1ml×1次,再给予芬太尼60μg/kg×4次;右美托咪定+芬太尼合剂组(DF1、DF2、DF3),根据组别设置分别给予大鼠皮下注射不同剂量的右美托咪定(12.5、25、50μg/kg)×1次,再给予芬太尼60μg/kg×4次。每次给药间隔15min。于注射前30min,注射后2、3、4h及1～5d对各组大鼠进行压尾机械伤害阈值(TFT)和足底热伤害潜时(PWL)疼痛行为学测试。给药后1d随机从每组取20只大鼠处死,取脊髓腰膨大区域,8份样本用于Western blotting测定α_(2A)肾上腺素受体(α_(2A)-AR)、一氧化氮合酶(iNOS)的表达,4份样本用于ELISA法测定P物质水平,8份样本用于免疫荧光法观察星形胶质细胞和小胶质细胞标志物胶质纤维酸性蛋白(GFAP)和离子钙接头蛋白1(Iba-1)的表达。结果 F、DF组的TFT及PWL值在注射后2～4h高于NS组,而F、DF1组在1～3d低于NS组,在1d时点最为显著,第4天恢复至NS组水平;DF2、DF3组在1～5d与NS组比较无明显差异。Westernblotting结果显示,与NS组比较,F、DF1组α_(2A)-AR表达下降、iNOS表达升高(P<0.05),与F组相比,DF2、DF3组α_(2A)-AR表达升高(P<0.05)、iNOS表达下降(P<0.05);ELISA结果表示,与F组比较,DF三个组P物质表达下降(P<0.05);免疫荧光法检测结果显示,F组GFAP和Iba-1阳性表达的细胞数高于NS及DF组(P<0.05)。结论右美托咪定可通过促进α_(2A)-AR表达,抑制星形胶质细胞和小胶质细胞的活化,降低iNOS和P物质的表达,从而减轻芬太尼诱导的痛觉过敏。
Objective To observe the changes in opioid induced hyperalgesia(OIH)after subcutaneous administration of dexmedetomidine,and explore the corresponding mechanism.Methods A hundred and thirty male SD rats were randomly divided into 5 groups(26 each):saline group(NS group),5 times of subcutaneous injection of saline 1 ml;fentanyl group(F group),subcutaneous injection of saline once,and 4 times injection of fentanyl 60μg/kg;dexmedetomidine+fentanyl mixture group(DF1,DF2 and DF3 group),hypodermic dexmedetomidine once with 12.5μg/kg,25μg/kg and 50μg/kg,respectively,and then 4 times injection of fentanyl 60μg/kg,with an interval of 15 min.Rats in each group were undergone the tests of tail flick threshold(TFT)and paw withdrawal latency(PWL)30 minutes before injection and 2,3,4 h and 1 to 5 days after injection.Twenty rats were randomly sacrificed from each group one day after drug administration to obtain the inflated spinal lumbar region.Eight samples were used to determine the expression of alpha-2 A adrenergic-receptor(α2A-AR)and inducible nitric oxide synthase(iNOS)by Western blotting,4 were measured the expression of substance P by ELISA,and 8 were used to observe the expression of astrocytes and microglia markers glial fibrillary acidic protein(GFAP)and Iba-1 by immunofluorescence.Results The behavioral results showed that the TFT and PWL were higher at 2 h to 4 h after injection in F group and DF groups than in NS group,but were lower at 1 to 3 days in F group and DF1 group than in NS group,the most significant difference appeared in the 1 st day and returned to the NS level at the 4 th day,while no statistical difference existed when compared between NS group with DF2 and DF3 groups at 1 to 5 days.Western blotting showed that compared with NS group,the expression ofα2A-AR decreased and iNOS increased in F and DF1 groups;compared with F group,the expression ofα2A-AR increased and iNOS decreased in DF2 and DF3 groups;ELISA results showed that compared with the F group,the expression of substance P decrease
作者
刘晴晴
魏碧玉
任鹏
刘永哲
郭航
孙立
郭文治
马亚群
高明龙
LIU Qing-qing;WEI Bi-yu;REN Peng;LIU Yong-zhe;GUO Hang;SUN Li;GUO Wen-zhi;MA Ya-qun;GAO Ming-long(Department of Anesthesiology,Shanxi Medical University,Taiyuan 030001,China;Department of Anesthesiology,Seventh Medical Center of PLA General Hospital,Beijing 100070,China)
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2018年第12期1024-1030,共7页
Medical Journal of Chinese People's Liberation Army
基金
北京市科技计划基金(Z161100000116074)~~
