国际口腔医学杂志 ›› 2020, Vol. 47 ›› Issue (6): 693-698.doi: 10.7518/gjkq.2020097

• 综述 • 上一篇    下一篇

药物性牙龈肥大的病因研究及治疗进展

李妍1,2(),孟琛达2,徐全臣1,2()   

  1. 1.青岛大学附属医院口腔科 青岛 266003
    2.青岛大学口腔医学院 青岛 266003
  • 收稿日期:2020-02-25 修回日期:2020-06-30 出版日期:2020-11-01 发布日期:2020-11-06
  • 通讯作者: 徐全臣
  • 作者简介:李妍,硕士,Email: 944058727@qq.com
  • 基金资助:
    山东省重点研发计划(2018GSF118150);国家自然科学基金(81500849)

Etiology and progress in the therapy of drug-induced gingival enlargement

Li Yan1,2(),Meng Chenda2,Xu Quanchen1,2()   

  1. 1. Dept. of Stomatology, Affiliated Hospital of Qingdao University, Qingdao 266003, China
    2. School of Stomatology, Qingdao University, Qingdao 266003, China
  • Received:2020-02-25 Revised:2020-06-30 Online:2020-11-01 Published:2020-11-06
  • Contact: Quanchen Xu
  • Supported by:
    Shandong Province Key Research and Development Plan(2018GSF118150);National Natural Science Foundation of China(81500849)

摘要:

药物性牙龈肥大(DIGE)是指长期服用某些药物而引起的牙龈纤维性增生和体积增大,严重危害患者的口腔健康。DIGE的病因尚未明确,治疗较为棘手。本文从炎症、Wnt/β-catenin信号通路、上皮间充质转化、整合素、基质金属蛋白酶等5个方面综述了DIGE病因学的研究进展,并从非手术治疗、手术治疗、药物治疗和辅助治疗等方面对其治疗方法的研究进展进行总结,以期对后续的研究及治疗提供一定的参考。

关键词: 药物性牙龈肥大, 硝苯地平, 苯妥英钠, 环孢素

Abstract:

Drug-induced gingival enlargement (DIGE) refers to gingival fibrosis hyperplasia and volume enlargement caused by long-term use of certain drugs. DIGE can cause serious damage to the oral health of patients. Its etiology is unclear, and treatment is difficult. This article will discuss the research progress of the etiology of DIGE from five aspects: inflammation, the Wnt/β-catenin signaling pathway, epithelial-mesenchymal transition, integrin, and matrix metalloproteinase. Therapeutic progress is reviewed from four aspects of non-surgical treatment, surgical treatment, drug therapy and adjuvant therapy to provide a certain reference value for subsequent research and treatment.

Key words: drug-induced gingival enlargement, nifedipine, phenytoin, cyclosporine

中图分类号: 

  • R781.4
[1] Ramírez-Rámiz A, Brunet-LLobet L, Lahor-Soler E, et al. On the cellular and molecular mechanisms of drug-induced gingival overgrowth[J]. Open Dent J, 2017,11:420-435.
doi: 10.2174/1874210601711010420 pmid: 28868093
[2] Bharti V, Bansal C. Drug-induced gingival overgrowth: the nemesis of gingiva unravelled[J]. J Indian Soc Periodontol, 2013,17(2):182-187.
doi: 10.4103/0972-124X.113066 pmid: 23869123
[3] Samudrala P, Chava VK, Chandana TS, et al. Drug-induced gingival overgrowth: a critical insight into case reports from over two decades[J]. J Indian Soc Periodontol, 2016,20(5):496-502.
doi: 10.4103/jisp.jisp_265_15
[4] Hatahira H, Abe J, Hane Y, et al. Drug-induced gingival hyperplasia: a retrospective study using spontaneous reporting system databases[J]. J Pharm Health Care Sci, 2017,3:19.
pmid: 28729910
[5] Li N, Liu N, Zhou J, et al. Inflammatory environment induces gingival tissue-specific mesenchymal stem cells to differentiate towards a pro-fibrotic phenotype[J]. Biol Cell, 2013,105(6):261-275.
doi: 10.1111/boc.201200064 pmid: 23521530
[6] Ganesh PR. Immunoexpression of interleukin-6 in drug- induced gingival overgrowth patients[J]. Contemp Clin Dent, 2016,7(2):140-145.
doi: 10.4103/0976-237X.183048
[7] Matsuda S, Okanobu A, Hatano S, et al. Relationship between periodontal inflammation and calcium channel blockers induced gingival overgrowth-a cross-sectional study in a Japanese population[J]. Clin Oral Investig, 2019,23(11):4099-4105.
doi: 10.1007/s00784-019-02846-8 pmid: 30771001
[8] Okanobu A, Matsuda S, Kajiya M, et al. A novel gingival overgrowth mouse model induced by the combination of CsA and ligature-induced inflam-mation[J]. J Immunol Methods, 2017,445:31-36.
pmid: 28274836
[9] MacDonald BT, Tamai K, He X. Wnt/β-catenin signaling: components, mechanisms, and diseases[J]. Dev Cell, 2009,17(1):9-26.
doi: 10.1016/j.devcel.2009.06.016 pmid: 19619488
[10] Königshoff M, Balsara N, Pfaff EM, et al. Functional Wnt signaling is increased in idiopathic pulmonary fibrosis[J]. PLoS One, 2008,3(5):e2142.
pmid: 18478089
[11] Russell JO, Monga SP. Wnt/β-catenin signaling in liver development, homeostasis, and pathobiology[J]. Annu Rev Pathol, 2018,13:351-378.
pmid: 29125798
[12] 崔硕, 王鹏, 高秀秋. Wnt1、β-catenin在硝苯地平引起的药物性牙龈增生中的表达[J]. 实用口腔医学杂志, 2017,33(1):78-82.
Cui S, Wang P, Gao XQ. Expression of Wnt1 and β- catenin in the gingival tissure with gingival overgrowth induced by nifedipine[J]. J Pract Stomatol, 2017,33(1):78-82.
[13] Yang F, Lu J, Yu YC, et al. Epithelial to mesenchymal transition in cyclosporine A-induced rat gingival overgrowth[J]. Arch Oral Biol, 2017,81:48-55.
doi: 10.1016/j.archoralbio.2017.04.024 pmid: 28472720
[14] Fu MM, Chin YT, Fu E, et al. Role of transforming growth factor-beta1 in cyclosporine-induced epi-thelial-to-mesenchymal transition in gingival epithe-lium[J]. J Periodontol, 2015,86(1):120-128.
doi: 10.1902/jop.2014.130285 pmid: 25272978
[15] Tsai CH, Yu CC, Lee SS, et al. Upregulation of Slug expression by cyclosporine A contributes to the pathogenesis of gingival overgrowth[J]. J Formos Med Assoc, 2016,115(8):602-608.
doi: 10.1016/j.jfma.2016.04.001 pmid: 27287534
[16] Larjava H, Koivisto L, Heino J, et al. Integrins in periodontal disease[J]. Exp Cell Res, 2014,325(2):104-110.
doi: 10.1016/j.yexcr.2014.03.010 pmid: 24662197
[17] Gürkan A, Emingil G, Afacan B, et al. Alpha 2 in-tegrin gene (ITGA2) polymorphism in renal transplant recipients with and without drug induced gingival overgrowth[J]. Arch Oral Biol, 2014,59(3):283-288.
doi: 10.1016/j.archoralbio.2013.12.003 pmid: 24581850
[18] 康颖竹, 郭淑娟, 刘程程, 等. 整合素α2β1与药物性牙龈增生相关性的研究进展[J]. 华西口腔医学杂志, 2017,35(1):99-103.
Kang YZ, Guo SJ, Liu CC, et al. Research progression of the relationship between integrin alpha2beta1 and drug-induced gingival overgrowth[J]. West China J Stomatol, 2017,35(1):99-103.
[19] Sardarian A, Andisheh Tadbir A, Zal F, et al. Altered oxidative status and integrin expression in cyclos-porine A-treated oral epithelial cells[J]. Toxicol Mech Methods, 2015,25(2):98-104.
doi: 10.3109/15376516.2014.990595 pmid: 25418342
[20] Johanson M, Zhao XR, Huynh-Ba G, et al. Matrix metalloproteinases, tissue inhibitors of matrix me-talloproteinases, and inflammation in cyclosporine A-induced gingival enlargement: a pilot in vitro study using a three-dimensional model of the human oral mucosa[J]. J Periodontol, 2013,84(5):634-640.
pmid: 22934840
[21] Dannewitz B, Edrich C, Tomakidi P, et al. Elevated gene expression of MMP-1, MMP-10, and TIMP-1 reveal changes of molecules involved in turn-over of extracellular matrix in cyclosporine-induced gingival overgrowth[J]. Cell Tissue Res, 2006,325(3):513-522.
pmid: 16670920
[22] Li WL, Wu CH, Yang J, et al. Local inflammation alters MMP-2 and MMP-9 gelatinase expression associated with the severity of nifedipine-induced gingival overgrowth: a rat model study[J]. Inflam-mation, 2015,38(4):1517-1528.
[23] Nazemisalman B, Sajedinejad N, Darvish S, et al. Evaluation of inductive effects of different concen-trations of cyclosporine A on MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2 in fetal and adult human gingival fibroblasts[J]. J Basic Clin Physiol Pharmacol, 2019,30(3). doi: 10.1515/jbcpp-2018-0176.
doi: 10.1515/jbcpp-2017-0218 pmid: 30375348
[24] Ritchhart C, Joy A. Reversal of drug-induced gingival overgrowth by UV-mediated apoptosis of gingival fibroblasts—an in vitro study[J]. Ann Anat, 2018,217:7-11.
doi: 10.1016/j.aanat.2018.01.001 pmid: 29427738
[25] Camargo PM, Melnick PR, Pirih FQ, et al. Treatment of drug-induced gingival enlargement: aesthetic and functional considerations[J]. Periodontol 2000, 2001,27:131-138.
pmid: 11551304
[26] Castronovo G, Liani G, Fedon A, et al. The effect of nonsurgical periodontal treatment on the severity of drug-induced gingival overgrowth in transplant patients[J]. Quintessence Int, 2014,45(2):115-124.
doi: 10.3290/j.qi.a31013 pmid: 24389563
[27] Raizada S, Varghese JM, Bhat KM, et al. Isolated gingival overgrowths: a review of case series[J]. Contemp Clin Dent, 2016,7(2):265-268.
pmid: 27307683
[28] Bán Á, Pintér E, Kun J. Proper oral health can pro-tect from developing gingival hyperplasia induced by calcium channel blockers[J]. Orv Hetil, 2018,159(29):1183-1187.
doi: 10.1556/650.2018.31088 pmid: 30008237
[29] Sam G, Sebastian SC. Nonsurgical management of nifedipine induced gingival overgrowth[J]. Case Rep Dent, 2014: 741402.
[30] Gawron K, Łazarz-Bartyzel K, Potempa J, et al. Gin-gival fibromatosis: clinical, molecular and therapeutic issues[J]. Orphanet J Rare Dis, 2016,11:9.
doi: 10.1186/s13023-016-0395-1 pmid: 26818898
[31] Ballini A, Scattarella A, Crincoli V, et al. Surgical treatment of gingival overgrowth with 10 years of follow-up[J]. Head Face Med, 2010,6:19.
doi: 10.1186/1746-160X-6-19 pmid: 20704737
[32] Campos L, Gallottini M, Pallos D, et al. High-power diode laser on management of drug-induced gin-gival overgrowth: report of two cases and long-term follow-up[J]. J Cosmet Laser Ther, 2018,20(4):215-219.
pmid: 29351498
[33] Muralikrishna T, Kalakonda B, Gunupati S, et al. Laser-assisted periodontal management of drug-induced gingival overgrowth under general anesthesia: a viable option[J]. Case Rep Dent, 2013,2013:387453.
doi: 10.1155/2013/387453 pmid: 23819068
[34] Ranga Rao S, Subbarayan R, Ajitkumar S, et al. 4PBA strongly attenuates endoplasmic reticulum stress, fibrosis, and mitochondrial apoptosis markers in cyclosporine treated human gingival fibroblasts[J]. J Cell Physiol, 2018,233(1):60-66.
doi: 10.1002/jcp.25836 pmid: 28158898
[35] Ma S, Liu W, Liu P, et al. Tanshinone ⅡA treatment alleviated the rat gingival connective tissue overgrowth induced by cyclosporine A[J]. J Periodont Res, 2016,51(5):567-576.
doi: 10.1111/jre.2016.51.issue-5
[36] Hirsch R, Deng H, Laohachai MN. Azithromycin in periodontal treatment: more than an antibiotic[J]. J Periodont Res, 2012,47(2):137-148.
doi: 10.1111/jre.2012.47.issue-2
[37] Kim JY, Park SH, Cho KS, et al. Mechanism of azithromycin treatment on gingival overgrowth[J]. J Dent Res, 2008,87(11):1075-1079.
doi: 10.1177/154405910808701110 pmid: 18946018
[38] Ratre MS, Mehta DS. Effect of azithromycin on gingival overgrowth induced by cyclosporine A + nifedipine combination therapy: a morphometric analysis in rats[J]. J Indian Soc Periodontol, 2016,20(4):396-401.
pmid: 28298821
[39] López-González MJ, Luis E, Fajardo O, et al. TRPA1 channels mediate human gingival fibroblast response to phenytoin[J]. J Dent Res, 2017,96(7):832-839.
pmid: 28571526
[40] Takeuchi R, Hiratsuka K, Arikawa K, et al. Possible pharmacotherapy for nifedipine-induced gingival overgrowth: 18α-glycyrrhetinic acid inhibits human gingival fibroblast growth[J]. Br J Pharmacol, 2016,173(5):913-924.
doi: 10.1111/bph.13410 pmid: 26676684
[1] 肖娟 赵慧综述 刘福祥审校. 苯妥英钠性牙龈增生的病理机制[J]. 国际口腔医学杂志, 2012, 39(2): 260-264.
[2] 刘培红综述马肃审校. 环孢素诱导牙龈上皮细胞增生的机制[J]. 国际口腔医学杂志, 2009, 36(1): 81-81~83.
[3] 文海燕综述 束 蓉审校. 硝苯地平介导药物性牙龈增生的研究进展[J]. 国际口腔医学杂志, 2009, 36(1): 84-84~87.
[4] 黄雅玲1, 李升2综述 杨明华1审校. 药物性牙龈增生发病机制的研究进展[J]. 国际口腔医学杂志, 2008, 35(4): 414-414~417.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 张新春. 桩冠修复与无髓牙的保护[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 王昆润. 长期单侧鼻呼吸对头颅发育有不利影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[3] 彭国光. 颈淋巴清扫术中颈交感神经干的解剖变异[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 杨凯. 淋巴化疗的药物运载系统及其应用现状[J]. 国际口腔医学杂志, 1999, 26(05): .
[5] 康非吾. 种植义齿下部结构生物力学研究进展[J]. 国际口腔医学杂志, 1999, 26(05): .
[6] 柴枫. 可摘局部义齿用Co-Cr合金的激光焊接[J]. 国际口腔医学杂志, 1999, 26(04): .
[7] 孟姝,吴亚菲,杨禾. 伴放线放线杆菌产生的细胞致死膨胀毒素及其与牙周病的关系[J]. 国际口腔医学杂志, 2005, 32(06): 458 -460 .
[8] 费晓露,丁一,徐屹. 牙周可疑致病菌对口腔黏膜上皮的粘附和侵入[J]. 国际口腔医学杂志, 2005, 32(06): 452 -454 .
[9] 赵兴福,黄晓晶. 变形链球菌蛋白组学研究进展[J]. 国际口腔医学杂志, 2008, 35(S1): .
[10] 庞莉苹,姚江武. 抛光和上釉对陶瓷表面粗糙度、挠曲强度及磨损性能的影响[J]. 国际口腔医学杂志, 2008, 35(S1): .