Resveratrol attenuates morphine antinociceptive tolerance via SIRT1 regulation in the rat spinal cord
Resveratrol attenuates morphine antinociceptive tolerance via SIRT1 regulation in the rat spinal cord
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DOI：
10.1016/j.neulet.2014.02.022
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发表时间：
2014-04-30
影响因子：
2.5
通讯作者：
Guo, Qulian
中科院分区：
文献类型：
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作者：
He, Xin;Ou, Peng;Guo, Qulian
近年来，研究人员开始更加关注Sirtuin 1（SIRT1，一种III类组蛋白脱乙酰酶）在疼痛中的作用。然而，很少有研究探讨 SIRT1 在慢性吗啡耐受中的作用。本研究的目的是探讨脊髓SIRT1和乙酰组蛋白H3(Ac-H3)在大鼠慢性吗啡耐受中的作用。通过每天两次鞘内 (i.t.) 注射吗啡 (10 jig) 连续 6 天诱导慢性吗啡耐受。对照大鼠接受生理盐水(NS)。然后在第7-13天注射白藜芦醇(Res，一种SIRT1兴奋剂，30μg i.t.)或二甲亚砜(DMSO，10μl i.t.)。评估热缩爪阈值以确定吗啡（10μg）的镇痛效果。采用gRT-PCR、Western blotting和免疫组化检测SIRT1和Global Ac-H3的表达。给予吗啡 6 天可诱导稳定的抗伤害耐受性、脊髓背角 SIRT1 表达下调和 Ac-H3 表达上调。与吗啡耐受 (MT) 组相比，第 7 天至第 13 天的白藜芦醇治疗增加了 SIRT1 表达，抑制了整体 Ac-H3 表达，并显着逆转了吗啡镇痛耐受。这些结果表明白藜芦醇通过上调脊髓背角中 SIRT1 的表达来逆转吗啡耐受。脊髓中的 SIRT1 和整体 Ac-H3 可能在慢性吗啡耐受机制中发挥重要作用。 (C) 2014 Elsevier Ireland Ltd. 保留所有权利。
In recent years, researchers have begun to pay more attention to the role of Sirtuin 1 (SIRT1, a class III histone deacetylase) in pain. However, little research has been conducted examining the involvement of SIRT1 in chronic morphine tolerance. The aim of this study was to investigate the role of spinal SIRT1 and acetyl-histone H3(Ac-H3) in chronic morphine tolerance in rats. Chronic morphine tolerance was induced by twice-daily intrathecal (i.t.) injections of morphine (10 jig) for 6 days. Control rats received normal saline (NS). Resveratrol (Res, a SIRT1 stimulant, 30 mu g i.t.) or dimethyl sulfoxide (DMSO, 10 Ill i.t.) was then injected on days 7-13. The thermal paw withdrawal threshold was assessed to determine the analgesic effects of morphine (10 mu g). gRT-PCR, western blotting and immunohistochemistry were used to detect the expression of SIRT1 and global Ac-H3. Administration of morphine for 6 days induced a stabilized antinociceptive tolerance, down-regulated SIRT1 expression and up-regulated Ac-H3 expression in the spinal dorsal horn. Resveratrol treatment from day 7 to 13 increased SIRT1 expression, suppressed global Ac-H3 expression compared to the morphine tolerance (MT) group, and significantly reversed morphine antinociceptive tolerance. These results suggest that resveratrol reversed morphine tolerance by upregulating the expression of SIRT1 in the spinal dorsal horn. SIRT1 and global Ac-H3 in the spinal cord may play an important role in the mechanisms of chronic morphine tolerance. (C) 2014 Elsevier Ireland Ltd. All rights reserved.