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本文引用的文献

1
The involvement of a cyclooxygenase 1 gene-derived protein in the antinociceptive action of paracetamol in mice.环氧化酶1基因衍生蛋白在对乙酰氨基酚对小鼠的镇痛作用中的参与。
Eur J Pharmacol. 2006 May 24;538(1-3):57-65. doi: 10.1016/j.ejphar.2006.03.061. Epub 2006 Apr 1.
2
Methylprednisolone reduces pain, emesis, and fatigue after breast augmentation surgery: a single-dose, randomized, parallel-group study with methylprednisolone 125 mg, parecoxib 40 mg, and placebo.甲泼尼龙可减轻隆胸手术后的疼痛、呕吐和疲劳：一项使用125毫克甲泼尼龙、40毫克帕瑞昔布和安慰剂的单剂量、随机、平行组研究。
Anesth Analg. 2006 Feb;102(2):418-25. doi: 10.1213/01.ane.0000194358.46119.e1.
3
Glucocorticoids: exemplars of multi-tasking.糖皮质激素：身兼多职的典范。
Br J Pharmacol. 2006 Jan;147 Suppl 1(Suppl 1):S258-68. doi: 10.1038/sj.bjp.0706456.
4
Effects of co-administered dexamethasone and diclofenac potassium on pain, swelling and trismus following third molar surgery.联合使用地塞米松和双氯芬酸钾对第三磨牙手术后疼痛、肿胀和牙关紧闭的影响。
Head Face Med. 2005 Nov 7;1:11. doi: 10.1186/1746-160X-1-11.
5
Stimulus-dependent specificity for annexin 1 inhibition of the inflammatory nociceptive response: the involvement of the receptor for formylated peptides.膜联蛋白1对炎症性伤害性反应抑制作用的刺激依赖性特异性：甲酰化肽受体的参与
Pain. 2004 May;109(1-2):52-63. doi: 10.1016/j.pain.2004.01.009.
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Dexamethasone promotes toxicity in U937 cells exposed to otherwise nontoxic concentrations of peroxynitrite: pivotal role for lipocortin 1-mediated inhibition of cytosolic phospholipase A2.地塞米松在U937细胞暴露于原本无毒浓度的过氧亚硝酸盐时会促进毒性：脂皮质素1介导的对胞质磷脂酶A2的抑制起关键作用。
Mol Pharmacol. 2004 Apr;65(4):964-72. doi: 10.1124/mol.65.4.964.
7
Modulation of inflammation and response to dexamethasone by Annexin 1 in antigen-induced arthritis.膜联蛋白1在抗原诱导性关节炎中对炎症的调节及对地塞米松的反应
Arthritis Rheum. 2004 Mar;50(3):976-84. doi: 10.1002/art.20201.
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Glucocorticoids up-regulate constitutive interleukin-10 production by human monocytes.
Clin Exp Allergy. 2004 Mar;34(3):406-12. doi: 10.1111/j.1365-2222.2004.01824.x.
9
Continuous brain-derived neurotrophic factor (BDNF) infusion after methylprednisolone treatment in severe spinal cord injury.甲基强的松龙治疗严重脊髓损伤后持续输注脑源性神经营养因子（BDNF）
J Korean Med Sci. 2004 Feb;19(1):113-22. doi: 10.3346/jkms.2004.19.1.113.
10
Aberrant inflammation and resistance to glucocorticoids in annexin 1-/- mouse.膜联蛋白1基因敲除小鼠中的异常炎症反应及对糖皮质激素的抵抗
FASEB J. 2003 Feb;17(2):253-5. doi: 10.1096/fj.02-0239fje. Epub 2002 Dec 3.

膜联蛋白A1基因敲除小鼠对伤害性疼痛的易感性增加，表明膜联蛋白A1具有脊髓抗伤害感受作用。

Increased susceptibility of annexin-A1 null mice to nociceptive pain is indicative of a spinal antinociceptive action of annexin-A1.

作者信息

Ayoub S S, Yazid S, Flower R J

机构信息

Centre for Biochemical Pharmacology, William Harvey Research Institute, St Bart's and the London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London, UK.

出版信息

Br J Pharmacol. 2008 Jul;154(5):1135-42. doi: 10.1038/bjp.2008.166. Epub 2008 May 12.

DOI:10.1038/bjp.2008.166
PMID:18469846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2451045/
Abstract

BACKGROUND AND PURPOSE

Annexin-A1 (ANXA1), a glucocorticoid-regulated protein, mediates several of the anti-inflammatory actions of the glucocorticoids. Previous studies demonstrated that ANXA1 is involved in pain modulation. The current study, using ANXA1 knockout mice (ANXA1-/-), is aimed at addressing the site and mechanism of the modulatory action of ANXA1 as well as possible involvement of ANXA1 in mediating the analgesic action of glucocorticoids.

EXPERIMENTAL APPROACH

The acetic acid-induced writhing response was performed in ANXA1-/- and wild-type (ANXA1+/+) mice with spinal and brain levels of prostaglandin E2 (PGE2) examined in both genotypes. The effect of the ANXA1 peptomimetic Ac2-26 as well as methylprednisolone on the writhing response and on spinal cord PGE2 of ANXA1+/+ and ANXA1-/- was compared. The expression of proteins involved in PGE2 synthesis, cytosolic phospholipase A2 (cPLA2) and cyclooxygenases (COXs), in the spinal cord of ANXA1+/+ and ANXA1-/- was also compared.

KEY RESULTS

ANXA1-/- mice exhibited a significantly greater writhing response and increased spinal cord levels of PGE2 compared with ANXA1+/+ mice. Ac2-26 produced analgesia and reduced spinal PGE2 levels in ANXA1+/+ and ANXA1-/- mice, whereas methylprednisolone reduced the writhing response and spinal PGE2 levels in ANXA1+/+, but not in ANXA1-/- mice. The expression of cPLA2, COX-1, COX-2 and COX-3 in spinal cord tissues was upregulated in ANXA1-/-compared with ANXA1+/+.

CONCLUSIONS AND IMPLICATIONS

We conclude that ANXA1 protein modulates nociceptive processing at the spinal level, by reducing synthesis of PGE2 by modulating cPLA2 and/or COX activity. The analgesic activity of methylprednisolone is mediated by spinal ANXA1.

摘要

背景与目的

膜联蛋白A1（ANXA1）是一种糖皮质激素调节蛋白，介导糖皮质激素的多种抗炎作用。先前的研究表明，ANXA1参与疼痛调节。本研究使用ANXA1基因敲除小鼠（ANXA1-/-），旨在探讨ANXA1调节作用的部位和机制，以及ANXA1在介导糖皮质激素镇痛作用中可能的参与情况。

实验方法

在ANXA1-/-和野生型（ANXA1+/+）小鼠中进行醋酸诱导的扭体反应，并检测两种基因型小鼠脊髓和脑内前列腺素E2（PGE2）的水平。比较ANXA1拟肽Ac2-26以及甲基强的松龙对ANXA1+/+和ANXA1-/-小鼠扭体反应和脊髓PGE2的影响。还比较了ANXA1+/+和ANXA1-/-小鼠脊髓中参与PGE2合成的蛋白，即胞质磷脂酶A2（cPLA2）和环氧化酶（COXs）的表达。

主要结果

与ANXA1+/+小鼠相比，ANXA1-/-小鼠表现出明显更强的扭体反应，且脊髓中PGE2水平升高。Ac2-26在ANXA1+/+和ANXA1-/-小鼠中产生镇痛作用并降低脊髓PGE2水平，而甲基强的松龙在ANXA1+/+小鼠中降低扭体反应和脊髓PGE2水平，但在ANXA1-/-小鼠中无此作用。与ANXA1+/+相比，ANXA1-/-小鼠脊髓组织中cPLA2、COX-1、COX-2和COX-3的表达上调。

结论与意义

我们得出结论，ANXA1蛋白通过调节cPLA2和/或COX活性来减少PGE2的合成，从而在脊髓水平调节伤害性感受过程。甲基强的松龙的镇痛活性由脊髓中的ANXA1介导。