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摘要: 血红素氧合酶-1(hemeoxygenase-1, HO-1)是血红素代谢过程中的限速酶，催化血红素裂解生成等分子的一氧化碳(carbon monoxide, CO)、胆绿素和Fe2+。HO-1是一种公认的保护剂，具有抗炎、抗氧化的作用，并参与调控细胞增殖、凋亡、自噬等重要生命过程，对各种不同组织的创伤均具有保护作用。多项研究显示，HO-1在非甾体抗炎药(non-steroidal anti-inflammatory drugs, NSAIDs)相关性消化道损伤、炎症性肠病(inflammatory bowel disease, IBD)、肠缺血再灌注损伤、消化道肿瘤、胃瘫等多种消化道疾病中均有适应性表达，并起到保护胃肠组织和细胞的重要作用。本文就HO-1在消化道疾病防治中的作用及机制研究进行综述。Abstract: Hemeoxygenase-1 (HO-1) is a rate-limiting enzyme in heme metabolism, which cleaves heme into equimolar quantities of carbon monoxide (CO), biliverdin and Fe2+.HO-1 is a recognized protective agent, which has anti-inflammatory and antioxidant effects and participates in the regulation of cell proliferation, apoptosis, autophagy and other important life processes, and plays a protective role in various tissue injuries. Multiple studies have shown that HO-1 plays an important role in protecting gastrointestinal tissues and cells and has adaptive expression in a variety of gastrointestinal diseases including non-steroidal anti-inflammatory drugs (NSAIDs) related gastrointestinal injury, inflammatory bowel disease disease(IBD), intestinal ischemia-reperfusion injury, gastrointestinal tumor, gastroparesis. We reviewed the role and mechanism of HO-1 in the prevention and treatment of gastrointestinal diseases.
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[1] Hayashi S, Omata Y, Sakamoto H, et al. Characterization of rat heme oxygenase-3 gene. Implication of processed Pseudogenes derived from heme oxygenase-2 gene[J]. Gene, 2004, 336(2): 241-250. DOI: 10.1016/j.gene.2004.04.002.
[2] Ewing JF, Maines MD. Histochemical localization of heme oxygenase-2 protein and mRNA expression in rat brain[J]. Brain Res Brain Res Protoc, 1997, 1(2): 165-174. DOI: 10.1016/s1385-299x(96)00027-x.
[3] Ryter SW. Heme oxygenase-1/carbon monoxide as modulators of autophagy and inflammation[J]. Arch Biochem Biophys, 2019, 678: 108186. DOI: 10.1016/j.abb.2019.108186.
[4] Alam J, Stewart D, Touchard C, et al. Nrf2, a Cap'n'Collar transcription factor, regulates induction of the heme oxygenase-1 gene[J]. J Biol Chem, 1999, 274(37): 26071-26078. DOI: 10.1074/jbc.274.37.26071.
[5] Sun JY, Hoshino H, Takaku K, et al. Hemoprotein Bach1 regulates enhancer availability of heme oxygenase-1 gene[J]. EMBO J, 2002, 21(19): 5216-5224. DOI: 10.1093/emboj/cdf516.
[6] Shan Y, Lambrecht RW, Donohue SE, et al. Role of Bach1 and Nrf2 in up-regulation of the heme oxygenase-1 gene by cobalt protoporphyrin[J]. FASEB J, 2006, 20(14): 2651-2653. DOI: 10.1096/fj.06-6346fje.
[7] Chen HH, Chen YT, Huang YW, et al. 4-Ketopinoresinol, a novel naturally occurring ARE activator, induces the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling[J]. Free Radic Biol Med, 2012, 52(6): 1054-1066. DOI: 10.1016/j.freeradbiomed.2011.12.012.
[8] Motohashi H, Yamamoto M. Carcinogenesis and transcriptional regulation through Maf recognition elements[J]. Cancer Sci, 2007, 98(2): 135-139. DOI: 10.1111/j.1349-7006.2006.00358.x.
[9] Suzuki H, Tashiro S, Hira S, et al. Heme regulates gene expression by triggering Crm1-dependent nuclear export of Bach1[J]. EMBO J, 2004, 23(13): 2544-2553. DOI: 10.1038/sj.emboj.7600248.
[10] Kondo K, Ishigaki Y, Gao JH, et al. Bach1 deficiency protects pancreatic β-cells from oxidative stress injury[J]. Am J Physiol Endocrinol Metab, 2013, 305(5): E641-E648. DOI: 10.1152/ajpendo.00120.2013.
[11] Takada T, Miyaki S, Ishitobi H, et al. Bach1 deficiency reduces severity of osteoarthritis through upregulation of heme oxygenase-1[J]. Arthritis Res Ther, 2015, 17: 285. DOI: 10.1186/s13075-015-0792-1.
[12] Wallace JL. How do NSAIDs cause ulcer disease?[J]. Baillieres Best Pract Res Clin Gastroenterol, 2000, 14(1): 147-159. DOI: 10.1053/bega.1999.0065.
[13] Song HJ, Shin CY, Oh TY, et al. Eupatilin with heme oxygenase-1-inducing ability protects cultured feline esophageal epithelial cells from cell damage caused by indomethacin[J]. Biol Pharm Bull, 2009, 32(4): 589-596. DOI: 10.1248/bpb.32.589.
[14] Bindu S, Mazumder S, Dey S, et al. Nonsteroidal anti-inflammatory drug induces proinflammatory damage in gastric mucosa through NF-κB activation and neutrophil infiltration: anti-inflammatory role of heme oxygenase-1 against nonsteroidal anti-inflammatory drug[J]. Free Radic Biol Med, 2013, 65: 456-467. DOI: 10.1016/j.freeradbiomed.2013.07.027.
[15] Uc A, Zhu XY, Wagner BA, et al. Heme oxygenase-1 is protective against nonsteroidal anti-inflammatory drug-induced gastric ulcers[J]. J Pediatr Gastroenterol Nutr, 2012, 54(4): 471-476. DOI: 10.1097/MPG.0b013e3182334fdf.
[16] Aburaya M, Tanaka K, Hoshino T, et al. Heme oxygenase-1 protects gastric mucosal cells against non-steroidal anti-inflammatory drugs[J]. J Biol Chem, 2006, 281(44): 33422-33432. DOI: 10.1074/jbc.M602074200.
[17] Yoda Y, Amagase K, Kato S, et al. Prevention by lansoprazole, a proton pump inhibitor, of indomethacin-induced small intestinal ulceration in rats through induction of heme oxygenase-1[J]. J Physiol Pharmacol, 2010, 61(3): 287-294.
[18] Song HJ, Shin CY, Oh TY, et al. The protective effect of eupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: involvement of HO-1 and ERK[J]. J Ethnopharmacol, 2008, 118(1): 94-101. DOI: 10.1016/j.jep.2008.03.010.
[19] Choi KM, Gibbons SJ, Nguyen TV, et al. Heme oxygenase-1 protects interstitial cells of Cajal from oxidative stress and reverses diabetic gastroparesis[J]. Gastroenterology, 2008, 135(6): 2055-2064, 2064. e1-2. DOI: 10.1053/j.gastro.2008.09.003.
[20] Tian LG, Song SN, Zhu BB, et al. Electroacupuncture at ST-36 protects interstitial cells of Cajal via sustaining heme oxygenase-1 positive M2 macrophages in the stomach of diabetic mice[J]. Oxid Med Cell Longev, 2018, 2018: 3987134. DOI: 10.1155/2018/3987134.
[21] Attuwaybi BO, Kozar RA, Moore-Olufemi SD, et al. Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury[J]. J Surg Res, 2004, 118(1): 53-57. DOI: 10.1016/j.jss.2004.01.010.
[22] Mallick IH, Winslet MC, Seifalian AM. Ischemic preconditioning of small bowel mitigates the late phase of reperfusion injury: heme oxygenase mediates cytoprotection[J]. Am J Surg, 2010, 199(2): 223-231. DOI: 10.1016/j.amjsurg.2009.01.011.
[23] Tamaki T, Konoeda Y, Yasuhara M, et al. Glutamine-induced heme oxygenase-1 protects intestines and hearts from warm ischemic injury[J]. Transplant Proc, 1999, 31(1-2): 1018-1019. DOI: 10.1016/s0041-1345(98)01882-x.
[24] Mallick IH, Yang WX, Winslet MC, et al. Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine[J]. World J Gastroenterol, 2005, 11(46): 7308-7313. DOI: 10.3748/wjg.v11.i46.7308.
[25] Yoshida T, Maulik N, Ho YS, et al. H(mox-1) constitutes an adaptive response to effect antioxidant cardioprotection: a study with transgenic mice heterozygous for targeted disruption of the Heme oxygenase-1 gene[J]. Circulation, 2001, 103(12): 1695-1701. DOI: 10.1161/01.cir.103.12.1695.
[26] Liu XL, Wei J, Peng DH, et al. Absence of heme oxygenase-1 exacerbates myocardial ischemia/reperfusion injury in diabetic mice[J]. Diabetes, 2005, 54(3): 778-784. DOI: 10.2337/diabetes.54.3.778.
[27] Scott JR, Cukiernik MA, Ott MC, et al. Low-dose inhaled carbon monoxide attenuates the remote intestinal inflammatory response elicited by hindlimb ischemia-reperfusion[J]. Am J Physiol Gastrointest Liver Physiol, 2009, 296(1): G9-G14. DOI: 10.1152/ajpgi.90243.2008.
[28] Nakao A, Kaczorowski DJ, Sugimoto R, et al. Application of heme oxygenase-1, carbon monoxide and biliverdin for the prevention of intestinal ischemia/reperfusion injury[J]. J Clin Biochem Nutr, 2008, 42(2): 78-88. DOI: 10.3164/jcbn.2008013.
[29] Nakao A, Kimizuka K, Stolz DB, et al. Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury[J]. Am J Pathol, 2003, 163(4): 1587-1598. DOI: 10.1016/S0002-9440(10)63515-8.
[30] Yun KJ, Choi SC, Oh JM. Expression of heme oxygenase-1 in ischemic colitis[J]. Taehan Sohwagi Hakhoe Chi, 2005, 45(5): 335-339.
[31] Wang WP, Guo X, Koo MW, et al. Protective role of heme oxygenase-1 on trinitrobenzene sulfonic acid-induced colitis in rats[J]. Am J Physiol Gastrointest Liver Physiol, 2001, 281(2): G586-G594. DOI: 10.1152/ajpgi.2001.281.2.G586.
[32] Paul G, Bataille F, Obermeier F, et al. Analysis of intestinal haem-oxygenase-1 (HO-1) in clinical and experimental colitis[J]. Clin Exp Immunol, 2005, 140(3): 547-555. DOI: 10.1111/j.1365-2249.2005.02775.x.
[33] Zhang LY, Zhang YJ, Zhong WW, et al. Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis by regulating Th17/Treg cell balance[J]. J Biol Chem, 2014, 289(39): 26847-26858. DOI: 10.1074/jbc.M114.590554.
[34] Naito Y, Takagi T, Yoshikawa T. Heme oxygenase-1: a new therapeutic target for inflammatory bowel disease[J]. Aliment Pharmacol Ther, 2004, 20(Suppl 1): 177-184. DOI: 10.1111/j.1365-2036.2004.01992.x.
[35] Khor TO, Huang MT, Kwon KH, et al. Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis[J]. Cancer Res, 2006, 66(24): 11580-11584. DOI: 10.1158/0008-5472.CAN-06-3562.
[36] Harusato A, Naito Y, Takagi T, et al. BTB and CNC homolog 1 (Bach1) deficiency ameliorates TNBS colitis in mice: role of M2 macrophages and heme oxygenase-1[J]. Inflamm Bowel Dis, 2013, 19(4): 740-753. DOI: 10.1097/MIB.0b013e3182802968.
[37] Hegazi RA, Rao KN, Mayle A, et al. Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway[J]. J Exp Med, 2005, 202(12): 1703-1713. DOI: 10.1084/jem.20051047.
[38] Zuckerbraun BS, Otterbein LE, Boyle P, et al. Carbon monoxide protects against the development of experimental necrotizing enterocolitis[J]. Am J Physiol Gastrointest Liver Physiol, 2005, 289(3): G607-G613. DOI: 10.1152/ajpgi.00055.2005.
[39] Takagi T, Naito Y, Uchiyama K, et al. Colonic insufflation with carbon monoxide gas inhibits the development of intestinal inflammation in rats[J]. Med Gas Res, 2012, 2(1): 23. DOI: 10.1186/2045-9912-2-23.
[40] Fukuda W, Takagi T, Katada K, et al. Anti-inflammatory effects of carbon monoxide-releasing molecule on trinitrobenzene sulfonic acid-induced colitis in mice[J]. Dig Dis Sci, 2014, 59(6): 1142-1151. DOI: 10.1007/s10620-013-3014-1.
[41] Sheikh SZ, Hegazi RA, Kobayashi T, et al. An anti-inflammatory role for carbon monoxide and heme oxygenase-1 in chronic Th2-mediated murine colitis[J]. J Immunol, 2011, 186(9): 5506-5513. DOI: 10.4049/jimmunol.1002433.
[42] Horváth K, Varga C, Berkó A, et al. The involvement of heme oxygenase-1 activity in the therapeutic actions of 5-aminosalicylic acid in rat colitis[J]. Eur J Pharmacol, 2008, 581(3): 315-323. DOI: 10.1016/j.ejphar.2007.12.004.
[43] Sun XM, Suzuki K, Nagata M, et al. Rectal administration of tranilast ameliorated acute colitis in mice through increased expression of heme oxygenase-1[J]. Pathol Int, 2010, 60(2): 93-101. DOI: 10.1111/j.1440-1827.2009.02490.x.
[44] Han KH, Park JM, Jeong M, et al. Heme oxygenase-1 induction and anti-inflammatory actions of Atractylodes macrocephala and Taraxacum herba extracts prevented colitis and was more effective than sulfasalazine in preventing relapse[J]. Gut Liver, 2017, 11(5): 655-666. DOI: 10.5009/gnl16496.
[45] Takagi T, Uchiyama K, Naito Y. The therapeutic potential of carbon monoxide for inflammatory bowel disease[J]. Digestion, 2015, 91(1): 13-18. DOI: 10.1159/000368765.
[46] Calkins BM. A meta-analysis of the role of smoking in inflammatory bowel disease[J]. Dig Dis Sci, 1989, 34(12): 1841-1854. DOI: 10.1007/BF01536701.
[47] Beaugerie L, Massot N, Carbonnel F, et al. Impact of cessation of smoking on the course of ulcerative colitis[J]. Am J Gastroenterol, 2001, 96(7): 2113-2116. DOI: 10.1111/j.1572-0241.2001.03944.x.
[48] Yang L, Shen L, Li Y, et al. Hyperoside attenuates dextran sulfate sodium-induced colitis in mice possibly via activation of the Nrf2 signalling pathway[J]. J Inflamm (Lond), 2017, 14: 25. DOI: 10.1186/s12950-017-0172-5.
[49] Zhang MZ, Xu CL, Liu DD, et al. Oral delivery of nanoparticles loaded with ginger active compound, 6-shogaol, attenuates ulcerative colitis and promotes wound healing in a murine model of ulcerative colitis[J]. J Crohns Colitis, 2018, 12(2): 217-229. DOI: 10.1093/ecco-jcc/jjx115.
[50] Ju SW, Ge Y, Li P, et al. Dietary quercetin ameliorates experimental colitis in mouse by remodeling the function of colonic macrophages via a heme oxygenase-1-dependent pathway[J]. Cell Cycle, 2018, 17(1): 53-63. DOI: 10.1080/15384101.2017.1387701.
[51] Tan Y, Zheng CQ. Effects of alpinetin on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium-induced ulcerative colitis mice[J]. Am J Med Sci, 2018, 355(4): 377-386. DOI: 10.1016/j.amjms.2018.01.002.
[52] Ren QG, Yang SL, Hu JL, et al. Evaluation of HO-1 expression, cellular ROS production, cellular proliferation and cellular apoptosis in human esophageal squamous cell carcinoma tumors and cell lines[J]. Oncol Rep, 2016, 35(4): 2270-2276. DOI: 10.3892/or.2016.4556.
[53] Yin YJ, Liu QJ, Wang B, et al. Expression and function of heme oxygenase-1 in human gastric cancer[J]. Exp Biol Med (Maywood), 2012, 237(4): 362-371. DOI: 10.1258/ebm.2011.011193.
[54] Yin HZ, Fang J, Liao L, et al. Upregulation of heme oxygenase-1 in colorectal cancer patients with increased circulation carbon monoxide levels, potentially affects chemotherapeutic sensitivity[J]. BMC Cancer, 2014, 14: 436. DOI: 10.1186/1471-2407-14-436.
[55] Andrés NC, Fermento ME, Gandini NA, et al. Heme oxygenase-1 has antitumoral effects in colorectal cancer: involvement of p53[J]. Exp Mol Pathol, 2014, 97(3): 321-331. DOI: 10.1016/j.yexmp.2014.09.012.
[56] Oláh G, Módis K, Törö G, et al. Role of endogenous and exogenous nitric oxide, carbon monoxide and hydrogen sulfide in HCT116 colon cancer cell proliferation[J]. Biochem Pharmacol, 2018, 149: 186-204. DOI: 10.1016/j.bcp.2017.10.011.
[57] Jun SY, Hong SM, Bae YK, et al. Clinicopathological and prognostic significance of heme oxygenase-1 expression in small intestinal adenocarcinomas[J]. Pathol Int, 2018, 68(5): 294-300. DOI:10.1111/pin.12657.
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