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出 处:《山东医药》2014年第28期14-16,共3页Shandong Medical Journal
基 金:山东省科技发展计划项目(2013GSF11863)
摘 要:目的:探讨黑皮质素受体拮抗剂(HS014)对吗啡耐受大鼠脊髓组织OX-42及肿瘤坏死因子α(TNF-α)表达的影响及意义。方法健康雄性SD大鼠30只,随机分为5组,每组6只,分别为吗啡耐受组( M组)、生理盐水组( N组)、HS014+吗啡组( HM组)、生理盐水+吗啡组( NM组)和HS014+生理盐水组( HN组),各组连续给药5 d。于第5天实验结束后,取各组大鼠L4~6段脊髓组织,采用免疫组织化学法检测脊髓组织OX-42、TNF-α。结果与N 组比较,M、HM、NM 组大鼠脊髓组织OX-42、TNF-α表达均增加,P 均<0.01;与M 组比较,HM 组大鼠脊髓组织OX-42、TNF-α表达下降,P 均<0.01;其余组间比较差异均无统计学意义(P 均>0.05)。结论吗啡耐受大鼠脊髓小胶质细胞被激活,表现为OX-42表达增加,并释放大量TNF-α;HS014能够减轻吗啡耐受,机制可能与其抑制吗啡引起的小胶质细胞激活及TNF-α释放有关。Objective To investigate of melanocortin receptor antagonist (HS014) on OX-42 and tumor necrosis fac-tor-α( TNF-α) expression in spinal cord tissues of morphine-tolerance rats .Methods Thirty adult male SD rats were ran-domly divided into 5 groups (n=6): morphine tolerance group (group M), normal saline group (group N), HS014+morphine group (group HM), normal saline +morphine group (group NM) and HS014+normal saline group (group HN) , each group was administered continuously for 5 d.All rats were sacrificed after the last dose on day 5 to obtain the L4-6 spinal cord tissues .The expression of TNF-αand OX-42 was examined by immunohistochemical technique .Results Compared with the group N , the expression of TNF-αand OX-42 was significantly increased in the groups M , HM and NM (all P〈0.01).Compared with group M, the expression of TNF-αand OX-42 was significantly decreased in the group HM (all P〈0.01).There was no significant differences between the other groups (all P〉0.05).Conclusions Chronic use of morphine can induce microglial activation which shows that the expression of OX -42 and TNF-αis increased.HS014 can attenuate the morphine tolerance , whose mechanism may be related to the inhibition of morphine-induced activation of mi-croglia and TNF-αrelease.
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