HS014对吗啡耐受大鼠脊髓组织 OX-42、TNF-α表达的影响及意义

摘要

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.%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。