新型抗炎介质消退素的生物效应及机制_West China Medical Journal

Authors：

 赵宇亮 , 张凌 , 杨济桥 ,  付平

四川大学华西医院肾脏内科（成都，610041）;

Corresponding author：

付平, Email: fupinghx@163.com

Keywords：

消退素; 抗炎; 生物效应; 机制

DOI：

10.7507/1002-0179.20140050

Video：

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消退素是一类具有抗炎效果的内源性多不饱和脂肪酸衍生物，可分为E类消退素、D类消退素、阿司匹林触发消退素等类型。消退素在多种组织器官的炎症中显示出较强的抗炎效果，同时还具有镇痛、抗纤维化、改善胰岛素抵抗等作用。而核因子-κB、丝裂原活化蛋白激酶、蛋白激酶B等通路可能介导上述生物效应。现就消退素的生物效应及机制的最新研究进展作一综述。

Citation： 赵宇亮, 张凌, 杨济桥, 付平. 新型抗炎介质消退素的生物效应及机制. West China Medical Journal, 2014, 29(1): 164-167. doi: 10.7507/1002-0179.20140050 Copy

1.	Serhan CN, Hong S, Gronert K, et al. Resolvins:a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals[J]. J Exp Med, 2002, 196(8):1025-1037.
2.	袁红梅, 万敬员, 张力. 促炎症消退新介质:消退素与保护素[J]. 生命科学, 2012, 24(1):54-57.
3.	Schwab JM, Chiang N, Arita M, et al. Resolvin E1 and protectin D1 activate inflammation-resolution programmes[J]. Nature, 2007, 447(7146):869-874.
4.	Weylandt KH, Chiu CY, Gomolka B, et al. Omega-3 fatty acids and their lipid mediators:towards an understanding of resolvin and protectin formation[J]. Prostaglandins Other Lipid Mediat, 2012, 97(3-4):73-82.
5.	Haas-Stapleton EJ, Lu Y, Hong S, et al. Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator resolvin E1[J]. PLoS One, 2007, 2(12):e1316.
6.	Lee CH. Resolvins as new fascinating drug candidates for inflammatory diseases[J]. Arch Pharm Res, 2012, 35(1):3-7.
7.	王彬, 张力, 闵苏. 消退素:内源性促炎症消退新介质[J]. 生命的化学, 2011, 31(5):756-759.
8.	Norling LV, Dalli J, Flower RJ, et al. Resolvin D1 limits polymorphonuclear leukocyte recruitment to inflammatory loci:receptor-dependent actions[J]. Arterioscler Thromb Vasc Biol, 2012, 32(8):1970-1978.
9.	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):1957-1969.
10.	Giera M, Ioan-Facsinay A, Toes R, et al. Lipid and lipid mediator profiling of human synovial fluid in rheumatoid arthritis patients by means of LC-MS/MS[J]. Biochim Biophys Acta, 2012, 1821(11):1415-1424.
11.	Wang B, Gong X, Wan JY, et al. Resolvin D1 protects mice from LPS-induced acute lung injury[J]. Pulm Pharmacol Ther, 2011, 24(4):434-441.
12.	Rogerio AP, Haworth O, Croze R, et al. Resolvin D1 and aspirin-triggered resolvin D1 promote resolution of allergic airways responses[J]. J Immunol, 2012, 189(4):1983-1991.
13.	Eickmeier O, Seki H, Haworth O, et al. Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury[J]. Mucosal Immunol, 2013, 6(2):256-266.
14.	Campbell EL, Louis NA, Tomassetti SE, et al. Resolvin E1 promotes mucosal surface clearance of neutrophils:a new paradigm for inflammatory resolution[J]. FASEB J, 2007, 21(12):3162-3170.
15.	Kim TH, Kim GD, Jin YH, et al. Omega-3 fatty acid-derived mediator, Resolvin E1, ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis in NC/Nga mice[J]. Int Immunopharmacol, 2012, 14(4):384-391.
16.	Recchiuti A, Krishnamoorthy S, Fredman G, et al. MicroRNAs in resolution of acute inflammation:identification of novel resolvin D1-miRNA circuits[J]. FASEB J, 2011, 25(2):544-560.
17.	Qu X, Zhang X, Yao J, et al. Resolvins E1 and D1 inhibit interstitial fibrosis in the obstructed kidney via inhibition of local fibroblast proliferation[J]. J Pathol, 2012, 228:506-519.
18.	Krishnamoorthy S, Recchiuti A, Chiang N, et al. Resolvin D1 binds human phagocytes with evidence for proresolving receptors[J]. Proc Natl Acad Sci USA, 2010, 107(4):1660-1665.
19.	Liao Z, Dong J, Wu W, et al. Resolvin D1 attenuates inflammation in lipopolysaccharide-induced acute lung injury through a process involving the PPARgamma/NF-kappaB pathway[J]. Respir Res, 2012, 13(1):110.
20.	El Kebir D, Gjorstrup P, Filep JG. Resolvin E1 promotes phagocytosis-induced neutrophil apoptosis and accelerates resolution of pulmonary inflammation[J]. Proc Natl Acad Sci USA, 2012, 109(37):14983-14988.
21.	Ariel A, Fredman G, Sun YP, et al. Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression[J]. Nat Immunol, 2006, 7(11):1209-1216.
22.	Vassiliou EK, Kesler OM, Tadros JH, et al. Bone marrow-derived dendritic cells generated in the presence of resolvin E1 induce apoptosis of activated CD4⁺ T cells[J]. J Immunol, 2008, 181(7):4534-4544.
23.	Krishnamoorthy S, Recchiuti A, Chiang N, et al. Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs[J]. Am J Pathol, 2012, 180(5):2018-2027.
24.	Fredman G, Li Y, Dalli J, et al. Self-limited versus delayed resolution of acute inflammation:temporal regulation of pro-resolving mediators and microRNA[J]. Sci Rep, 2012(2):639.
25.	Xu ZZ, Zhang L, Liu T, et al. Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions[J]. Nat Med, 2010, 16(5):592-597.
26.	Huang L, Wang CF, Serhan CN, et al. Enduring prevention and transient reduction of postoperative pain by intrathecal resolvin D1[J]. Pain, 2011, 152(3):557-565.
27.	Xu ZZ, Ji RR. Resolvins are potent analgesics for arthritic pain[J]. Br J Pharmacol, 2011, 164(2):274-277.
28.	Xu ZZ, Berta T, Ji RR. Resolvin E1 inhibits neuropathic pain and spinal cord microglial activation following peripheral nerve injury[J]. J Neuroimmune Pharmacol, 2013, 8(1):37-41.
29.	Bang S, Yoo S, Yang TJ, et al. Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception[J]. Br J Pharmacol, 2010, 161(3):707-720.
30.	Xu ZZ, Berta T, Ji RR. Resolvin e1 inhibits neuropathic pain and spinal cord microglial activation following peripheral nerve injury[J]. J Neuroimmune Pharmacol, 2013, 8(1):37-41.
31.	Bang S, Yoo S, Yang TJ, et al. 17(R)-resolvin D1 specifically inhibits transient receptor potential ion channel vanilloid 3 leading to peripheral antinociception[J]. Br J Pharmacol, 2012, 165(3):683-692.
32.	Lima-Garcia JF, Dutra RC, da Silva K, et al. The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats[J]. Br J Pharmacol, 2011, 164(2):278-293.
33.	Feng QX, Feng F, Feng XY, et al. Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia, phosphorylation of NMDA receptors, and cytokines expression in the thoracic spinal dorsal horn[J]. BMC Gastroenterol, 2012, 12(1):148.
34.	Duffield JS, Hong S, Vaidya VS, et al. Resolvin D series and protectin D1 mitigate acute kidney injury[J]. J Immunol, 2006, 177(9):5902-5911.
35.	Zhang X, Qu X, Sun YB, et al. Resolvin D1 protects podocytes in adriamycin-induced nephropathy through modulation of 14-3-3beta acetylation[J]. PLoS One, 2013, 8(6):e67471.
36.	Yang J, Eiserich JP, Cross CE, et al. Metabolomic profiling of regulatory lipid mediators in sputum from adult cystic fibrosis patients[J]. Free Radic Biol Med, 2012, 53(1):160-171.
37.	Titos E, Rius B, Gonzalez-Periz A, et al. Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype[J]. J Immunol, 2011, 187(10):5408-5418.
38.	Lund T, Mangsbo SM, Scholz H, et al. Resolvin E1 reduces proinflammatory markers in human pancreatic islets in vitro[J]. Exp Clin Endocrinol Diabetes, 2010, 118(4):237-244.
39.	Tang Y, Zhang MJ, Hellmann J, et al. Proresolution therapy for the treatment of delayed healing of diabetic wounds[J]. Diabetes, 2013, 62(2):618-627.

1. Serhan CN, Hong S, Gronert K, et al. Resolvins:a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals[J]. J Exp Med, 2002, 196(8):1025-1037.
2. 袁红梅, 万敬员, 张力. 促炎症消退新介质:消退素与保护素[J]. 生命科学, 2012, 24(1):54-57.
3. Schwab JM, Chiang N, Arita M, et al. Resolvin E1 and protectin D1 activate inflammation-resolution programmes[J]. Nature, 2007, 447(7146):869-874.
4. Weylandt KH, Chiu CY, Gomolka B, et al. Omega-3 fatty acids and their lipid mediators:towards an understanding of resolvin and protectin formation[J]. Prostaglandins Other Lipid Mediat, 2012, 97(3-4):73-82.
5. Haas-Stapleton EJ, Lu Y, Hong S, et al. Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator resolvin E1[J]. PLoS One, 2007, 2(12):e1316.
6. Lee CH. Resolvins as new fascinating drug candidates for inflammatory diseases[J]. Arch Pharm Res, 2012, 35(1):3-7.
7. 王彬, 张力, 闵苏. 消退素:内源性促炎症消退新介质[J]. 生命的化学, 2011, 31(5):756-759.
8. Norling LV, Dalli J, Flower RJ, et al. Resolvin D1 limits polymorphonuclear leukocyte recruitment to inflammatory loci:receptor-dependent actions[J]. Arterioscler Thromb Vasc Biol, 2012, 32(8):1970-1978.
9. 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):1957-1969.
10. Giera M, Ioan-Facsinay A, Toes R, et al. Lipid and lipid mediator profiling of human synovial fluid in rheumatoid arthritis patients by means of LC-MS/MS[J]. Biochim Biophys Acta, 2012, 1821(11):1415-1424.
11. Wang B, Gong X, Wan JY, et al. Resolvin D1 protects mice from LPS-induced acute lung injury[J]. Pulm Pharmacol Ther, 2011, 24(4):434-441.
12. Rogerio AP, Haworth O, Croze R, et al. Resolvin D1 and aspirin-triggered resolvin D1 promote resolution of allergic airways responses[J]. J Immunol, 2012, 189(4):1983-1991.
13. Eickmeier O, Seki H, Haworth O, et al. Aspirin-triggered resolvin D1 reduces mucosal inflammation and promotes resolution in a murine model of acute lung injury[J]. Mucosal Immunol, 2013, 6(2):256-266.
14. Campbell EL, Louis NA, Tomassetti SE, et al. Resolvin E1 promotes mucosal surface clearance of neutrophils:a new paradigm for inflammatory resolution[J]. FASEB J, 2007, 21(12):3162-3170.
15. Kim TH, Kim GD, Jin YH, et al. Omega-3 fatty acid-derived mediator, Resolvin E1, ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis in NC/Nga mice[J]. Int Immunopharmacol, 2012, 14(4):384-391.
16. Recchiuti A, Krishnamoorthy S, Fredman G, et al. MicroRNAs in resolution of acute inflammation:identification of novel resolvin D1-miRNA circuits[J]. FASEB J, 2011, 25(2):544-560.
17. Qu X, Zhang X, Yao J, et al. Resolvins E1 and D1 inhibit interstitial fibrosis in the obstructed kidney via inhibition of local fibroblast proliferation[J]. J Pathol, 2012, 228:506-519.
18. Krishnamoorthy S, Recchiuti A, Chiang N, et al. Resolvin D1 binds human phagocytes with evidence for proresolving receptors[J]. Proc Natl Acad Sci USA, 2010, 107(4):1660-1665.
19. Liao Z, Dong J, Wu W, et al. Resolvin D1 attenuates inflammation in lipopolysaccharide-induced acute lung injury through a process involving the PPARgamma/NF-kappaB pathway[J]. Respir Res, 2012, 13(1):110.
20. El Kebir D, Gjorstrup P, Filep JG. Resolvin E1 promotes phagocytosis-induced neutrophil apoptosis and accelerates resolution of pulmonary inflammation[J]. Proc Natl Acad Sci USA, 2012, 109(37):14983-14988.
21. Ariel A, Fredman G, Sun YP, et al. Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression[J]. Nat Immunol, 2006, 7(11):1209-1216.
22. Vassiliou EK, Kesler OM, Tadros JH, et al. Bone marrow-derived dendritic cells generated in the presence of resolvin E1 induce apoptosis of activated CD4⁺ T cells[J]. J Immunol, 2008, 181(7):4534-4544.
23. Krishnamoorthy S, Recchiuti A, Chiang N, et al. Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs[J]. Am J Pathol, 2012, 180(5):2018-2027.
24. Fredman G, Li Y, Dalli J, et al. Self-limited versus delayed resolution of acute inflammation:temporal regulation of pro-resolving mediators and microRNA[J]. Sci Rep, 2012(2):639.
25. Xu ZZ, Zhang L, Liu T, et al. Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions[J]. Nat Med, 2010, 16(5):592-597.
26. Huang L, Wang CF, Serhan CN, et al. Enduring prevention and transient reduction of postoperative pain by intrathecal resolvin D1[J]. Pain, 2011, 152(3):557-565.
27. Xu ZZ, Ji RR. Resolvins are potent analgesics for arthritic pain[J]. Br J Pharmacol, 2011, 164(2):274-277.
28. Xu ZZ, Berta T, Ji RR. Resolvin E1 inhibits neuropathic pain and spinal cord microglial activation following peripheral nerve injury[J]. J Neuroimmune Pharmacol, 2013, 8(1):37-41.
29. Bang S, Yoo S, Yang TJ, et al. Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception[J]. Br J Pharmacol, 2010, 161(3):707-720.
30. Xu ZZ, Berta T, Ji RR. Resolvin e1 inhibits neuropathic pain and spinal cord microglial activation following peripheral nerve injury[J]. J Neuroimmune Pharmacol, 2013, 8(1):37-41.
31. Bang S, Yoo S, Yang TJ, et al. 17(R)-resolvin D1 specifically inhibits transient receptor potential ion channel vanilloid 3 leading to peripheral antinociception[J]. Br J Pharmacol, 2012, 165(3):683-692.
32. Lima-Garcia JF, Dutra RC, da Silva K, et al. The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats[J]. Br J Pharmacol, 2011, 164(2):278-293.
33. Feng QX, Feng F, Feng XY, et al. Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia, phosphorylation of NMDA receptors, and cytokines expression in the thoracic spinal dorsal horn[J]. BMC Gastroenterol, 2012, 12(1):148.
34. Duffield JS, Hong S, Vaidya VS, et al. Resolvin D series and protectin D1 mitigate acute kidney injury[J]. J Immunol, 2006, 177(9):5902-5911.
35. Zhang X, Qu X, Sun YB, et al. Resolvin D1 protects podocytes in adriamycin-induced nephropathy through modulation of 14-3-3beta acetylation[J]. PLoS One, 2013, 8(6):e67471.
36. Yang J, Eiserich JP, Cross CE, et al. Metabolomic profiling of regulatory lipid mediators in sputum from adult cystic fibrosis patients[J]. Free Radic Biol Med, 2012, 53(1):160-171.
37. Titos E, Rius B, Gonzalez-Periz A, et al. Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype[J]. J Immunol, 2011, 187(10):5408-5418.
38. Lund T, Mangsbo SM, Scholz H, et al. Resolvin E1 reduces proinflammatory markers in human pancreatic islets in vitro[J]. Exp Clin Endocrinol Diabetes, 2010, 118(4):237-244.
39. Tang Y, Zhang MJ, Hellmann J, et al. Proresolution therapy for the treatment of delayed healing of diabetic wounds[J]. Diabetes, 2013, 62(2):618-627.

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