选择性Ⅰ型组蛋白去乙酰化酶抑制剂对蜜蜂毒诱致的大鼠自发痛和热痛敏的抑制作用（英文）

发布时间：2018-05-27 09:35

本文选题：蜜蜂毒 + 组蛋白去乙酰化酶　；参考：《生理学报》2015年05期

【摘要】：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。
[Abstract]:In order to determine the efficacy of histone deacetylase (HDAC) inhibitor in relieving peripheral inflammatory pain, the analgesic effects of two selective type I HDAC inhibitors, MS-275 and MGCD0103, were studied by subcutaneous injection of bee venom into the plantar of rats. The honeybee venom model can present a variety of pain manifestations, including persistent spontaneous pain related behavior, primary heat and mechanical pain sensitivity, and mirror thermal pain sensitivity. Intrathecal administration of 60 nmol/20 渭 L MS-275 and MGCD0103 could significantly inhibit the persistent spontaneous pain and primary thermal pain induced by bee venom, but had no significant effect on the primary mechanical pain sensitivity and mirror thermal sensitivity. The overexpression of HDAC1 and HDAC2 induced by subcutaneous injection of bee venom was completely inhibited by early intrathecal administration of MS-275. This study provides new evidence to prove that epigenetic regulation of histone hypoacetylated chromatin structure mediated by HDAC1/2 is involved in continuous spontaneous pain and thermal pain induced by bee venom. The results showed that type I HDAC inhibitor had a good preventive effect on the occurrence of peripheral inflammatory pain.
【作者单位】：首都医科大学基础医学院疼痛生物医学研究所;第四军医大学唐都医院疼痛生物医学研究所暨功能性脑疾病研究所;中国人民解放军脑应激与行为重点实验室;北京脑疾病研究院;
【基金】：supported by the National Natural Science Foundation of China(No.81171049) the National Basic Research Development Program of China(No.2011CB504100,2013CB835100) the National Key Technology R&D Program of China(No.2013BAI04B04) the Twelfth Five-Year Project of China(No.AWS12J004)
【分类号】：R965

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