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1.湖南中医药大学,长沙 410208
2.湖南中医药大学 第一附属医院,长沙 410007
Published:05 June 2023,
Published Online:01 July 2022,
Received:29 April 2022,
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孙豪娴,孙贵香,邱丽婷等.基于Nrf2/HO-1通路的中医药干预溃疡性结肠炎研究进展[J].中国实验方剂学杂志,2023,29(11):224-230.
SUN Haoxian,SUN Guixiang,QIU Liting,et al.Chinese Medicine Intervention in Ulcerative Colitis Based on Nrf2/HO-1 Pathway: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(11):224-230.
孙豪娴,孙贵香,邱丽婷等.基于Nrf2/HO-1通路的中医药干预溃疡性结肠炎研究进展[J].中国实验方剂学杂志,2023,29(11):224-230. DOI: 10.13422/j.cnki.syfjx.20221827.
SUN Haoxian,SUN Guixiang,QIU Liting,et al.Chinese Medicine Intervention in Ulcerative Colitis Based on Nrf2/HO-1 Pathway: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(11):224-230. DOI: 10.13422/j.cnki.syfjx.20221827.
溃疡性结肠炎(UC)是临床常见的一种慢性消化系统疾病,其病情反复且治疗难度大,发病机制复杂,与氧化应激反应相关。核转录因子E
2
相关因子2(Nrf2)是抗氧化反应中的重要因子,可调控其下游血红素加氧-1(HO-1)的表达,发挥维持机体氧化还原稳态的作用。UC的病程中Nrf2与HO-1的生物活性及含量水平均下降,组织抗氧化和抗炎能力减弱,肠上皮细胞损伤,肠黏膜屏障破坏。目前西医临床上主要以控制炎症和缓解症状治疗为主,虽有一定疗效,但存在停药后易复发、长期用药不良反应多等问题。研究表明,中医药治疗手段丰富,治疗方法灵活,在UC的防治上有广阔的应用前景。近年来,以Nrf2/HO-1通路为切入点,中医药领域开展了大量关于UC中该信号的基础和临床实验,结果表明Nrf2/HO-1通路是中医药治疗UC的重要潜在靶点。基于虚实夹杂的病因病机,中医药以清热解毒燥湿、活血化瘀止痛、益气补中温里和标本兼治等法调控Nrf2/HO-1通路,提高组织抗氧化应激能力,维持促炎因子与抗炎因子平衡,缓解炎症反应,发挥对UC的治疗作用。该文总结和分析了中医药靶向Nrf2/HO-1信号通路干预UC的机制和作用,以期为科研人员更为全面认识中医药对UC中Nrf2/HO-1通路的作用机制提供帮助,旨在推动今后中医药合理运用于临床UC的防治。
Ulcerative colitis (UC) is a common chronic digestive system disease in clinic. The disease is repeated and difficult to treat, and the pathogenesis is complex, which is related to oxidative stress response. Nuclear factor E
2
-related factor 2 (Nrf2) is an important factor in antioxidant reaction, which regulates the expression of downstream heme oxygen-1 (HO-1), and plays a role in maintaining redox homeostasis. In the course of UC, the biological activity and content of Nrf2 and HO-1 are decreased, the antioxidant and anti-inflammatory abilities of tissues are weakened, the intestinal epithelial cells are damaged, and the intestinal mucosal barrier is destroyed. At present, western medicine mainly focuses on controlling inflammation and alleviating symptoms in clinical treatment. Although it has a certain effect, there are many problems such as easy recurrence after drug withdrawal and long-term side effects. Studies have shown that Chinese medicine has rich and flexible therapeutic methods and has broad application prospects in the prevention and treatment of UC. In recent years, with Nrf2/HO-1 pathway as the entry point, a large number of basic and clinical experiments on this signal in UC have been carried out in the field of Chinese medicine, and the results show that the intervention of Nrf2/HO-1 pathway is an important potential target for the treatment of UC by Chinese medicines. Based on the etiology and pathogenesis of deficiency-excess in complexity, Chinese medicine regulates Nrf2/HO-1 pathway by clearing heat and detoxifying dampness, activating blood circulation to remove stasis and relieve pain, invigorating Qi, tonifying middle, and warming interior, and treating both symptoms and root causes, to improve the tissue's ability to resist oxidative stress, maintain the balance between pro-inflammatory factors and anti-inflammatory factors, relieve inflammatory response, and play a therapeutic role in UC. This paper summarized and analyzed the effect of Chinese medicine targeting the Nrf2/HO-1 signaling pathway on interfering with UC and its mechanism. The purpose of this study is to provide references for researchers to have a more comprehensive understanding of the mechanism of Chinese medicines in the Nrf2/HO-1 signaling pathway in UC and promote the rational application of Chinese medicines in the prevention and treatment of UC in the future.
中医药核转录因子E2相关因子2/血红素加氧-1溃疡性结肠炎研究进展
Chinese medicinenuclear factor E2-related factor 2/heme oxygen-1ulcerative colitisresearch progress
中华医学会消化病学分会炎症性肠病学组.炎症性肠病诊断与治疗的共识意见(2018年·北京)[J].中国实用内科杂志,2018,38(9):796-813.
中华中医药学会脾胃病分会.溃疡性结肠炎中医诊疗专家共识意见(2017)[J].中华中医药杂志,2017,32(8):3585-3589.
WANG R, DING X, TIAN Z, et al. Body composition changes and related factors in patients with ulcerative colitis: A retrospective single-center study in China [J]. Med Sci Monit, 2022, 28: e933942.
YU F Y, HUANG S G, ZHANG H Y, et al. Comparison of 5-hydroxytryptophan signaling pathway characteristics in diarrhea-predominant irritable bowel syndrome and ulcerative colitis [J]. World J Gastroenterol, 2016, 22(12): 3451-3459.
CHANGLIN Z, YING Z, SHUHUA Z, et al. Research on the protective effect of MiR-185-3p mediated by Huangqin-Tang decoction (HQT) on the epithelial barrier function of ulcerative colitis [J]. Evid Based Complement Alternat Med, 2021, 2021: 4775606.
RAHABI M, JACQUEMIN G, PRAT M, et al. Divergent roles for macrophage C-type lectin receptors, Dectin-1 and mannose receptors, in the intestinal inflammatory response [J]. Cell Rep, 2020, 30(13): 4386-4398.
刘晓桐, 顾立梅. 夏军权教授基于“浊毒”理论治疗活动期溃疡性结肠炎经验 [J]. 河北中医, 2021, 43(11): 1896-1899.
DE CRISTOFARO E, SALVATORI S, MARAFINI I, et al. Long-term risk of colectomy in patients with severe ulcerative colitis responding to intravenous corticosteroids or infliximab [J]. J Clin Med, 2022, 11(6): 1679.
GRAY K J, GIBBS J E. Adaptive immunity, chronic inflammation and the clock [J]. Semin Immunopathol, 2022, 44(2): 209-224.
HU Y, YE Z, SHE Y, et al. Efficacy and safety of probiotics combined with traditional chinese medicine for ulcerative colitis: A systematic review and Meta-analysis [J]. Front Pharmacol, 2022, doi: 10.3389/fphar.2022.844961http://dx.doi.org/10.3389/fphar.2022.844961.
LIU H, JOHNSTON L J, WANG F, et al. Triggers for the Nrf2/ARE signaling pathway and its nutritional regulation: Potential therapeutic applications of ulcerative colitis [J]. Int J Mol Sci, 2021, 22(21): 11411.
孙凯. 基于Nrf2/HO-1通路探讨结肠癌前病变中医分型及姜黄素干预结肠癌机制 [D]. 扬州: 扬州大学, 2021.
WANG R, LUO Y, LU Y, et al. Maggot extracts alleviate inflammation and oxidative stress in acute experimental colitis via the activation of Nrf2 [J]. Oxid Med Cell Longev, 2019, doi: 10.1155/2019/4703253http://dx.doi.org/10.1155/2019/4703253.
GUO F, TSAO R, LI C, et al. Green Pea (Pisum sativum L.) hull polyphenol extracts ameliorate DSS-induced colitis through Keap1/Nrf2 pathway and gut microbiota modulation [J]. Foods, 2021, 10(11): 2765.
HAYES J D, DINKOVA-KOSTOVA A T. Oncogene-stimulated congestion at the KEAP1 stress signaling Hub allows bypass of NRF2 and induction of NRF2-target genes that promote tumor survival [J]. Cancer Cell, 2017, 32(5): 539-541.
CHEN L, RAN Q, XIANG Y, et al. Co-activation of PKC-delta by CRIF1 modulates oxidative stress in bone marrow multipotent mesenchymal stromal cells after irradiation by phosphorylating NRF2 Ser40 [J]. Theranostics, 2017, 7(10): 2634-2648.
LIN Y, ZHENG X, CHEN J, et al. Protective effect of Bruguiera gymnorrhiza (L.) Lam. fruit on dextran sulfate sodium-induced ulcerative colitis in mice: Role of Keap1/Nrf2 pathway and gut microbiota [J]. Front Pharmacol, 2019, doi: 10.3389/fphar.2019.01602http://dx.doi.org/10.3389/fphar.2019.01602.
MARINHO S, ILLANES M, AVILA-ROMAN J, et al. Anti-inflammatory effects of rosmarinic acid-loaded nanovesicles in acute colitis through modulation of NLRP3 inflammasome [J]. Biomolecules, 2021, 11(2): 162.
BAI X, GOU X, CAI P, et al. Sesamin enhances Nrf2-mediated protective defense against oxidative stress and inflammation in colitis via Akt and ERK activation [J]. Oxid Med Cell Longev, 2019, doi: 10.1155/2019/2432416http://dx.doi.org/10.1155/2019/2432416.
HSIEH Y H, KIM Y, WU A G, et al. Isothiocyanate-enriched moringa seed extract alleviates ulcerative colitis symptoms in mice [J]. PLoS One, 2017, 12(9): e0184709.
陈韵之. 秦皮甲素对溃疡性结肠炎小鼠肠黏膜的抗炎作用的研究 [D]. 锦州: 锦州医科大学, 2020.
马涛. Nrf-2在溃疡性结肠炎病灶组织中的表达及其与抗氧化酶含量、组织损伤程度的相关性 [J]. 海南医学院学报, 2017, 23(13): 1783-1786.
伍建中. 美洲大蠊提取物对DSS诱导UC小鼠氧化应激及NRF2/HO-1通路的影响 [D]. 大理: 大理大学, 2021.
YU Y, ZHENG C, LU X, et al. GB1a Ameliorates ulcerative colitis via regulation of the NF-kappaB and Nrf2 signaling pathways in an experimental model [J]. Front Med (Lausanne), 2021, doi: 10.3389/fmed.2021.654867http://dx.doi.org/10.3389/fmed.2021.654867.
张阳, 王允亮, 王志斌, 等. 溃疡性结肠炎病机特点探讨 [J]. 中医杂志, 2022, 63(5): 488-490.
张娇娇, 张帆, 余星星, 等. 溃疡性结肠炎发病机制及中西医治疗研究进展 [J]. 辽宁中医药大学学报, 2021, 23(1): 70-74.
罗淑娟, 陈小芬, 林逸婷, 等. 健脾清热活血方介导keap-1-Nrf2信号调控claudin-2表达干预溃疡性结肠炎模型大鼠实验研究 [J]. 中国中医急症, 2021, 30(11): 1924-1928.
LEE J J, KIM K H, KIM E J, et al. Anti-inflammatory activity of the decoction of Forsythia suspensa (Thunb.) Vahl is related to Nrf2 and A20 [J]. J Ethnopharmacol, 2018, 227: 97-104.
ZHAO P, PIAO X, PAN L, et al. Forsythia suspensa extract attenuates lipopolysaccharide-induced inflammatory liver injury in rats via promoting antioxidant defense mechanisms [J]. Anim Sci J, 2017, 88(6): 873-881.
CHAO L, LIN J, ZHOU J, et al. Polyphenol rich forsythia suspensa extract alleviates DSS-induced ulcerative colitis in mice through the Nrf2-NLRP3 pathway [J]. Antioxidants (Basel), 2022, 11(3): 475.
YANG H, YUE Y, LI Y, et al. Geniposide attenuates dextran sulfate sodium-induced colitis in mice via Nrf-2/HO-1/NF-kappaB pathway [J]. Ann Palliat Med, 2020, 9(5): 2826-2836.
杨超. 基于FXR栀子治疗溃疡性结肠炎的物质基础及作用机制研究 [D]. 南昌: 江西中医药大学, 2020.
JIA L, XUE K, LIU J, et al. Anticolitic effect of berberine in rat experimental model: Impact of PGE2/p38 MAPK pathways [J]. Mediators Inflamm, 2020, 2020:9419085.
LI H, FAN C, LU H, et al. Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions [J]. Acta Pharm Sin B, 2020, 10(3): 447-461.
谭悦. 山姜素对溃疡性结肠炎肠上皮屏障作用的影响 [D]. 沈阳: 中国医科大学, 2018.
周江韬. 鸦胆子苦醇自微乳对溃疡性结肠炎的治疗作用研究 [D]. 广州: 广州中医药大学, 2018.
JEON Y D, LEE J H, LEE Y M, et al. Puerarin inhibits inflammation and oxidative stress in dextran sulfate sodium-induced colitis mice model [J]. Biomed Pharmacother, 2020, doi: 10.1016/j.biopha.2020.109847http://dx.doi.org/10.1016/j.biopha.2020.109847.
吕兴. 紫地榆提取物对溃疡性结肠炎大鼠的防治作用及机制研究 [D]. 大理: 大理大学, 2020.
CHEN M, LV Z, ZHANG W, et al. Triptolide suppresses airway goblet cell hyperplasia and Muc5ac expression via NF-kappaB in a murine model of asthma [J]. Mol Immunol, 2015, 64(1): 99-105.
CHEN M, SHI J T, LV Z Q, et al. Triptolide inhibits TGF-beta1 induced proliferation and migration of rat airway smooth muscle cells by suppressing NF-kappaB but not ERK1/2 [J]. Immunology, 2014, 144(3):486-494.
TANG B, ZHU J, ZHANG B, et al. Therapeutic potential of triptolide as an anti-inflammatory agent in dextran sulfate sodium-induced murine experimental colitis [J]. Front Immunol, 2020, doi: 10.3389/fimmu.2020.592084http://dx.doi.org/10.3389/fimmu.2020.592084.
KHODIR A E, SAID E, ATIF H, et al. Targeting Nrf2/HO-1 signaling by crocin: Role in attenuation of AA-induced ulcerative colitis in rats [J]. Biomed Pharmacother, 2019, 110: 389-399.
CHAPARALA A, TASHKANDI H, CHUMANEVICH A A, et al. Molecules from American ginseng suppress colitis through nuclear factor erythroid-2-related factor 2 [J]. Nutrients, 2020, 12(6): 1850.
ZHANG M, XU C, LIU D, 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.
刘冬羽. 甘草总黄酮及甘草查尔酮A对溃疡性结肠炎的治疗作用及其分子机制研究 [D]. 北京: 北京协和医学院, 2016.
刘億, 葛巍, 刘雪珂, 等. 四神丸对慢性结肠炎大鼠结肠组织相关因子表达的影响 [J]. 中华中医药学刊, 2019, 37(2): 330-333,530-531.
张雪侠, 金建闻, 刘长河, 等. Nrf2/HO-1通路在四神丸保护溃疡性结肠炎小鼠模型肠道损伤中的作用 [J]. 中国中药杂志, 2021, 46(16): 4187-4192.
娄余, 肖运婷, 朱莹, 等. 基于NF-κB信号通路的溃结宁膏穴位敷贴对溃疡性结肠炎大鼠结肠黏膜炎症反应的影响 [J]. 中国中医药信息杂志, 2021, 28(4): 75-80.
王生华,朱莹,王燚霈,等.基于Nrf2通路探讨溃结宁膏穴位敷贴治疗溃疡性结肠炎的作用机制[J].中国中西医结合杂志,2021,41(8):951-958.
张庚鑫, 杜海洋, 王平, 等. 基于16S rRNA测序研究葛根芩连汤对菌群失调性腹泻大鼠肠道菌群结构的影响 [J]. 中国实验方剂学杂志, 2021, 27(11): 19-26.
吴亿晗, 成颜芬, 王迪, 等. 葛根芩连汤三氯甲烷提取物缓解伊立替康所致肠毒性的作用机制分析 [J]. 中国实验方剂学杂志, 2021, 27(16): 16-23.
林川,王菲,王鸿卿,等.葛根苓连汤及配伍调控Nrf2/NQO1信号通路抑制溃疡性结肠炎大鼠氧化应激损伤[J].中国实验方剂学杂志,2022,28(13):19-27.
祁燕, 袁志伟, 万春平, 等. 溃结康对溃疡性结肠炎小鼠NLRP3炎性体基因表达及下游炎性因子影响 [J]. 中华中医药学刊, 2020, 38(3): 229-233,275-278.
祁燕, 袁志伟, 万春平, 等. 溃结康对溃疡性结肠炎小鼠结肠抗氧化作用及 Nrf2/ARE信号通路的影响 [J]. 中药药理与临床, 2019, 35(2): 115-119.
方静, 陈江, 彭君伟, 等. 基于Nrf2通路探讨薏苡附子败酱散治疗溃疡性结肠炎的作用机制 [J]. 中国实验方剂学杂志, 2018, 24(13): 85-92.
梁国强, 陈江, 葛惠男, 等. 基于Nrf_2通路薏苡附子败酱散联合西药对葡聚糖硫酸钠盐诱导小鼠结肠炎黏膜修复的影响 [J]. 中国中西医结合消化杂志, 2021, 29(4): 234-239.
YUAN Z, YANG L, ZHANG X, et al. Huang-Lian-Jie-Du decoction ameliorates acute ulcerative colitis in mice via regulating NF-kappaB and Nrf2 signaling pathways and enhancing intestinal barrier function [J]. Front Pharmacol, 2019, doi: 10.3389/fphar.2019.01354http://dx.doi.org/10.3389/fphar.2019.01354.
袁子文. 黄连解毒汤治疗小鼠急性溃疡性结肠炎疗效的评价及其作用机制研究 [D]. 兰州: 甘肃农业大学, 2020.
庄帅星. 黄芩汤调控Nrf2通路对溃疡性结肠炎的抗氧化应激作用机制研究 [D]. 北京: 中国中医科学院, 2016.
马旭冉, 王彦礼, 邹迪新, 等. 黄芩汤调控Nrf2通路对溃疡性结肠炎大鼠氧化应激作用的影响 [J]. 药学学报, 2019, 54(4): 653-659.
郭子霞, 安子璇, 张健美, 等. 药物治疗溃疡性结肠炎的信号通路研究进展 [J]. 神经药理学报, 2020, 10(4): 41-50,57.
满光亮, 刘永艳, 梁国强. 大黄牡丹汤联合柳氮磺胺吡啶肠溶片对溃疡性结肠炎小鼠氧化应激及Kelch样环氧氯丙烷相关蛋白1-核因子E2相关因子2信号通路的影响 [J]. 河北中医, 2021, 43(3): 463-468.
王佳俊, 王建, 李勇, 等. 基于细胞信号通路探讨小檗碱治疗溃疡性结肠炎研究进展 [J]. 中国中药杂志, 2021, 46(1): 33-40.
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