消退素D2药物治疗研究进展

doi:10.3760/cma.j.issn.1007-1245.2022.17.033

摘要/Abstract

摘要： 消退素是近年来新发现的内源性促炎症消退介质，消退素D2通过与其受体G蛋白偶联受体18结合产生抗炎及镇痛作用，已在炎症疾病、疼痛疾病、神经系统疾病等领域受到越来越多的重视，且在呼吸系统、消化系统、心血管系统疾病及肿瘤疾病等其他领域显示出良好的应用前景，有望为临床新型药物研制提供一种新的方案。

关键词: 消退素D2, 炎症, 急慢性疼痛, 药物治疗

Abstract: Resolvin is a newly discovered endogenous proinflammatory mediator in recent years. Regressin D2 produces anti-inflammatory and analgesic effects by binding to its receptor G Protein-Coupled Receptors18. It has attracted more and more attention in inflammatory diseases, pain diseases, nervous system diseases, and other fields. It also shows excellent application prospects in other fields, such as respiratory system, digestive system, cardiovascular system diseases, and tumor diseases. It is expected to provide a new scheme for the development of new clinical drugs.

Key words: Resolvin D2, Inflammation, Acute and chronic pain, Medication

杨磊田德民. 消退素D2药物治疗研究进展[J]. 国际医药卫生导报, 2022, 28(17): 2512-2515.

Yang Lei, Tian Demin. Research progress on medication of resolvin D2[J]. International Medicine and Health Guidance News, 2022, 28(17): 2512-2515.

参考文献

[1] Spite M, Norling LV, Summers L, et al. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis[J]. Nature, 2009,461(7268):1287-1291. DOI: 10.1038/nature08541.
[2] Weng HR, Gao M, Maixner DW. Glycogen synthase kinase 3 beta regulates glial glutamate transporter protein expression in the spinal dorsal horn in rats with neuropathic pain[J]. Exp Neurol, 2014,252:18-27. DOI: 10.1016/j.expneurol.2013.11.018.
[3] Gu Z, Lamont GJ, Lamont RJ, et al. Resolvin D1, resolvin D2 and maresin 1 activate the GSK3β anti-inflammatory axis in TLR4-engaged human monocytes[J]. Innate Immun,2016,22(3):186-195. DOI: 10.1177/1753425916628618.
[4] Chiang N, Dalli J, Colas RA, et al. Identification of resolvin D2 receptor mediating resolution of infections and organ protection[J]. J Exp Med, 2015,212(8):1203-1217. DOI: 10.1084/jem.20150225.
[5] Lopategi A, Flores-Costa R, Rius B, et al. Frontline Science: Specialized proresolving lipid mediators inhibit the priming and activation of the macrophage NLRP3 inflammasome[J]. J Leukoc Biol, 2019, 105(1):25-36. DOI: 10.1002/JLB.3HI0517-206RR.
[6] Croasdell A, Sime PJ, Phipps RP. Resolvin D2 decreases TLR4 expression to mediate resolution in human monocytes[J]. FASEB J, 2016, 30(9): 3181-3193. DOI: 10.1096/fj.201600375R.
[7] Chiang N, De la Rosa X, Libreros S, et al. Novel resolvin D2 receptor axis in infectious inflammation[J]. J Immunol, 2017, 198(2): 842-851. DOI:10.4049/jimmunol.1601650.
[8] Castilla-Madrigal R, Gil-Iturbe E, López de Calle M, et al. DHA and its derived lipid mediators MaR1, RvD1 and RvD2 block TNF-α inhibition of intestinal sugar and glutamine uptake in Caco-2 cells[J]. J Nutr Biochem, 2020, 76: 108264. DOI:10.1016/j.jnutbio.2019.108264.
[9] Siddiqui YD, Omori K, Ito T, et al. Resolvin D2 induces resolution of periapical inflammation and promotes healing of periapical lesions in rat periapical periodontitis[J]. Front Immunol, 2019, 10: 307. DOI: 10.3389/fimmu.2019.00307.
[10] Mizraji G, Heyman O, Van Dyke TE, et al. Resolvin D2 restrains Th1 immunity and prevents alveolar bone loss in murine periodontitis[J]. Front Immunol, 2018, 9: 785. DOI: 10.3389/fimmu.2018.00785.
[11] Videla LA, Vargas R, Valenzuela R, et al. Combined administration of docosahexaenoic acid and thyroid hormone synergistically enhances rat liver levels of resolvins RvD1 and RvD2[J]. Prostaglandins Leukot Essent Fatty Acids, 2019, 140: 42-46. DOI: 10.1016/j.plefa.2018.11.013.
[12] Elmarakby AA, Ibrahim AS, Katary MA, et al. A dual role of 12/15-lipoxygenase in LPS-induced acute renal inflammation and injury[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2019, 1864(11): 1669-1680. DOI: 10.1016/j.bbalip.2019.07.009.
[13] Klein CP, Sperotto ND, Maciel IS, et al. Effects of D-series resolvins on behavioral and neurochemical changes in a fibromyalgia-like model in mice[J]. Neuropharmacology, 2014, 86: 57-66. DOI:10.1016/j.neuropharm.2014.05.043.
[14] Park CK, Xu ZZ, Liu T, et al. Resolvin D2 is a potent endogenous inhibitor for transient receptor potential subtype V1/A1, inflammatory pain, and spinal cord synaptic plasticity in mice: distinct roles of resolvin D1, D2, and E1[J]. J Neurosci, 2011, 31(50): 18433-18438. DOI: 10.1523/JNEUROSCI.4192-11.2011.
[15] Zhang LY, Liu ZH, Zhu Q, et al. Resolvin D2 relieving radicular pain is associated with regulation of inflammatory mediators, AKT/GSK-3β signal pathway and GPR18[J]. Neurochem Res, 2018, 43(12): 2384-2392. DOI: 10.1007/s11064-018-2666-9.
[16] Luo X, Gu Y, Tao X, et al. Resolvin D5 inhibits neuropathic and inflammatory pain in male but not female mice: distinct actions of d-Series resolvins in chemotherapy-induced peripheral neuropathy[J]. Front Pharmacol, 2019, 10: 745. DOI: 10.3389/fphar.2019.00745.
[17] Ye Y, Scheff NN, Bernabé D, et al. Anti-cancer and analgesic effects of resolvin D2 in oral squamous cell carcinoma[J]. Neuropharmacology, 2018, 139: 182-193. DOI: 10.1016/j.neuropharm.2018.07.016.
[18] Tian Y, Zhang Y, Zhang R, et al. Resolvin D2 recovers neural injury by suppressing inflammatory mediators expression in lipopolysaccharide-induced Parkinson's disease rat model[J]. Biochem Biophys Res Commun, 2015, 460(3): 799-805. DOI: 10.1016/j.bbrc.2015.03.109.
[19] Zuo G, Zhang D, Mu R, et al. Resolvin D2 protects against cerebral ischemia/reperfusion injury in rats[J]. Mol Brain, 2018, 11(1): 9. DOI:10.1186/s13041-018-0351-1.
[20] Ishikawa Y, Deyama S, Shimoda K, et al. Rapid and sustained antidepressant effects of resolvin D1 and D2 in a chronic unpredictable stress model[J]. Behav Brain Res, 2017, 332: 233-236. DOI:10.1016/j.bbr.2017.06.010.
[21] Bento AF, Claudino RF, Dutra RC, et al. Omega-3 fatty acid-derived mediators 17(R)-hydroxy docosahexaenoic acid, aspirin-triggered resolvin D1 and resolvin D2 prevent experimental colitis in mice[J]. J Immunol, 2011, 187(4): 1957-69. DOI:10.4049/jimmunol.1101305.
[22] Khaddaj-Mallat R, Sirois C, Sirois M, et al. Pro-resolving effects of resolvin D2 in LTD4 and TNF-α pre-treated human bronchi[J]. PLoS One, 2016, 11(12): e0167058. DOI:10.1371/journal.pone.0167058.
[23] Viola JR, Lemnitzer P, Jansen Y, et al. Resolving lipid mediators maresin 1 and resolvin D2 prevent atheroprogression in mice[J]. Circ Res, 2016, 119(9): 1030-1038. DOI:10.1161/CIRCRESAHA.116.309492.
[24] Zhang MJ, Sansbury BE, Hellmann J, et al. Resolvin D2 enhances postischemic revascularization while resolving inflammation[J]. Circulation, 2016, 134(9): 666-680. DOI:10.1161/CIRCULATIONAHA.116.021894.
[25] Botten N, Hodges RR, Li D, et al. Resolvin D2 elevates cAMP to increase intracellular [Ca2+] and stimulate secretion from conjunctival goblet cells[J]. FASEB J, 2019, 33(7): 8468-8478. DOI:10.1096/fj.201802467R.
[26] Pascoal LB, Bombassaro B, Ramalho AF, et al. Resolvin RvD2 reduces hypothalamic inflammation and rescues mice from diet-induced obesity[J]. J Neuroinflammation, 2017, 14(1): 5. DOI:10.1186/s12974-016-0777-2.
[27] Inoue Y, Liu YM, Otawara M, et al. Resolvin D2 limits secondary tissue necrosis after burn wounds in rats[J]. J Burn Care Res, 2018, 39(3): 423-432. DOI:10.1097/BCR.0000000000000617.
[28] Bohr S, Patel SJ, Sarin D, et al. Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model[J]. Wound Repair Regen, 2013, 21(1): 35-43. DOI:10.1111/j.1524-475X.2012.00853.x.
[29] Arany PR. The skinny on fats in wound healing[J]. J Invest Dermatol, 2018, 138(9): 1909-1910. DOI:10.1016/j.jid.2018.04.020.
[30] Hellmann J, Sansbury BE, Wong B, et al. Biosynthesis of D-Series resolvins in skin provides insights into their role in tissue repair[J]. J Invest Dermatol, 2018, 138(9): 2051-2060. DOI:10.1016/j.jid.2018.03.1498.
[31] Dong X, Gao J, Zhang CY, et al. Neutrophil membrane-derived nanovesicles alleviate inflammation to protect mouse brain injury from ischemic stroke[J]. ACS Nano, 2019, 13(2): 1272-1283. DOI:10.1021/acsnano.8b06572.
[32] Sulciner ML, Serhan CN, Gilligan MM, et al. Resolvins suppress tumor growth and enhance cancer therapy[J]. J Exp Med., 2018, 215(1): 115-140. DOI:10.1084/jem.20170681.
[33] Gu Z, Lamont GJ, Lamont RJ, et al. Resolvin D1, resolvin D2 and maresin 1 activate the GSK3β anti-inflammatory axis in TLR4-engaged human monocytes[J]. Innate Immun, 2016, 22(3): 186-195. DOI:10.1177/1753425916628618.
[34] Gc JB, Szlenk CT, Gao J, et al. Molecular dynamics simulations provide insight into the loading efficiency of proresolving lipid mediators resolvin D1 and D2 in cell membrane-derived nanovesicles[J]. Mol Pharm, 2020, 17(6):2155-2164. DOI:10.1021/acs.molpharmaceut.0c00299.