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为了明确I型组蛋白去乙酰化酶(histone deacetylase,HDAC)抑制剂对外周炎性痛的减轻是否有效,本实验采用对大鼠足底皮下注射蜜蜂毒的方法研究了两种选择性I型HDAC抑制剂MS-275和MGCD0103的镇痛作用。蜜蜂毒模型能够呈现多种疼痛表现型,包括持续性自发痛相关行为,原发性热和机械痛敏,以及镜像热痛敏。鞘内提前给予剂量为60 nmol/20μL的MS-275和MGCD0103能够显著抑制蜜蜂毒诱致的持续性自发痛和原发性热痛敏,而对原发性机械痛敏和镜像热痛敏无显著影响;而且,由皮下注射蜜蜂毒诱致的HDAC1和HDAC2的高表达通过鞘内提前给予MS-275得到了完全抑制。本研究为证明由HDAC1/2介导的组蛋白低乙酰化染色质结构的表观遗传学调控参与介导蜜蜂毒诱致的持续性自发痛和热痛敏提供了新的证据,并表明I型HDAC抑制剂对外周炎性痛的发生具有良好的预防效果。
In order to find out whether histone deacetylase (HDAC) inhibitors are effective in relieving peripheral inflammatory pain, two types of selective type I The analgesic effect of the HDAC inhibitors MS-275 and MGCD0103. The bee venom model is capable of exhibiting a variety of pain phenotypes, including persistent spontaneous pain-related behaviors, primary thermal and mechanical hyperalgesia, and mirrored thermal hyperalgesia. Intrathecal administration of MS-275 and MGCD0103 at a dose of 60 nmol / 20 μL significantly inhibited persistent spontaneous pain and primary thermal hyperalgesia induced by bee venom without significant effect on primary mechanical and thermal pain sensitivities ; And, the high expression of HDAC1 and HDAC2 induced by subcutaneous injection of bee venom was completely inhibited by pre-intrathecal MS-275 administration. This study provides new evidence to demonstrate that the epigenetic regulation of HDAC1 / 2-mediated histone hypoacetylation chromatin structure is involved in mediating bee venom-induced persistent spontaneous pain and thermal hyperalgesia and suggests that type I HDAC inhibitors have a good preventive effect on the occurrence of peripheral inflammatory pain.