重庆医学2017,Vol.46Issue(34):4771-4773,3.DOI:10.3969/j.issn.1671-8348.2017.34.005
鞘内注射右美托咪定对大鼠吗啡耐受及脊髓炎性反应的影响
Effects of intrathecal administration of dexmedetomidine on morphine tolerance and inflammatory response in rats
摘要
Abstract
Objective To investigate the effects of intrathecal dexmedetomidine administration on the development of morphine tolerance and spinal inflammatory responses.Methods Thirty-three male SD rats weighing 180~200 g were randomly divided into 3 groups (n=11):Saline group (group NS),Morphine group (group M) and Dexmedetomidine group (group Dex).Animals of group NS were intrathecally injected with 10 tμL of saline daily for seven days;Animals in group M were intrathecally injected with 15 μg of morphine daily for seven days;Animals in group Dex were intrathecally injected with a mixture of 15μg morphine and 1.5 μg dexmedetomidine daily for seven days.At 1,3,5 and 7 day of intrathecal injection,hot water tail-flick test were used to evaluate analgesic response to thermal stimuli.After the last episode of behavioral test,Western blot analysis was applied to determine the protein levels of Iba-1 (microglial marker),IL-1β,TNF-a and phospho-p38MAPK (p-p38) in the spinal cord.In addition,microglia in the spinal cord was immuno-stained with anti-Iba-1 antibody and the densities of microglia were calculated.Results In group M and Dex,the values of maximal possible effect (MPE) in tail-flick test decreased gradually along with repeated morphine administration (P<0.05).Compared with group NS,the values of MPE in tail-flick test at 1,3,5 and 7 day of morphine tolerance were higher in group M (P<0.05).Compared with group M,the values of MPE in tail-flick test at 3,5 and 7 day of morphine tolerance were higher in group Dex (P<0.05).Compared with group NS,the spinal protein levels of Iba-1,IL-1L TNF-α and p-p38 as well as the density of Iba-1 positive cells in group M were increased (P<0.05).However,Compared with group M,the of Iba-1,IL-1β,TNF-α and p-p38 as well as the density of Iba-1 positive cells were decreased(P<0.05).Conclusion Intrathecal dexmedetomidine administration can attenuate morphine tolerance by inhibiting microglia-mediated inflammatory responses in the spinal cord.关键词
右美托咪定/吗啡/药物耐受性/小胶质细胞/炎症Key words
dexmedetomidine/morphine/drug tolerance/drug tolerance/inflammatory分类
医药卫生引用本文复制引用
巩红岩,郑芳,左志超,刘景景,王庆志,赵国安..鞘内注射右美托咪定对大鼠吗啡耐受及脊髓炎性反应的影响[J].重庆医学,2017,46(34):4771-4773,3.基金项目
河南省医学科技攻关计划项目(201204026). (201204026)