二甲双胍对大鼠口腔黏膜溃疡的疗效之组织学评价

doi:10.13701/j.cnki.kqyxyj.2019.07.011

口腔医学研究 ›› 2019, Vol. 35 ›› Issue (7): 661-665.DOI: 10.13701/j.cnki.kqyxyj.2019.07.011

二甲双胍对大鼠口腔黏膜溃疡的疗效之组织学评价

梁兆佳, 贺嘉忻^#, 陈紫韵, 熊小琴, 霍昌宝, 林池灏, 刘晓明, 张君伟, 余挺^*

广州医科大学附属口腔医院·广州口腔疾病研究所·口腔医学重点实验室广东广州 510140

收稿日期:2018-11-05 出版日期:2019-07-25 发布日期:2019-07-24
通讯作者: 余挺,E-mail:dent_yu@163.com
作者简介:梁兆佳(1999~ ),男,广东南海人,学士,从事口腔黏膜病相关研究。贺嘉忻(1996~ ),男,广东台山人,学士,从事牙周病相关研究
基金资助:
广州医科大学大学生实验室开放项目(C195015024) 大学生科技创新项目(2017A069、2018C051) 国家级大学生创新创业训练计划(201810570016) 国家自然科学基金(81700985)

Therapeutic Potentials of Metformin in Management of Oral Mucosal Ulcer in Rats: a Histological Study

LIANG Zhaojia, HE Jiaxin^#, CHEN Ziyun, XIONG Xiaoqin, HUO Changbao, LIN Chihao, LIU Xiaoming, ZHANG Junwei, YU Ting^*

Key Laboratory of Oral Medicine,Guangzhou Institute of Oral Disease,Stomatology Hospital of Guangzhou Medical University,Guangzhou 510140, China.

Received:2018-11-05 Online:2019-07-25 Published:2019-07-24

摘要/Abstract

摘要： 目的:探索二甲双胍(MET)对口腔黏膜溃疡(OMU)的疗效。方法:创伤法在SD大鼠(n=24)两侧颊黏膜建立OMU模型。24 h后(d₁),左侧(MET侧)溃疡基底每天注射20 μmol/L MET溶液,右侧(对照侧)注射生理盐水,记录溃疡面积。d₂、d₄、d₇分别处死8只,行溃疡组织切片染色,分析新生上皮厚度和比例、结缔组织炎细胞数和胶原纤维含量。结果:d₁时,同侧溃疡面积均匀,两侧面积等大(P=0.935)。d₂~d₇,溃疡面积不断缩小(P<0.05),胶原纤维含量和新生上皮厚度不断上升;炎细胞数于d₂~d₄上升,d₄~d₇下降(P<0.05)。d₂~d₅,MET侧溃疡面积小于对照侧16%~37%(P<0.05),d₆~d₇则不显著。d₁~d₇,MET侧炎细胞数小于对照侧(P<0.05)。d₂~d₄,MET侧胶原纤维含量和新生上皮厚度高于对照侧(P<0.05),此优势在d₄~d₇不再显著。结论:MET对早期OMU有明显改善作用,可能与抑制炎症,促进组织修复有关

关键词: 二甲双胍, 口腔溃疡, 组织学, 上皮, 愈合

Abstract: Objective: To explore the effects of metformin (MET) on oral mucosal ulcer (OMU). Methods: OMU models were established with trauma at bilateral buccal mucosa in SD rats (n=24). After 24 hours (d₁), 20 μmol/L MET solution was injected into the ulcer base of left side (MET side) one time per day, with normal saline injected into the right side as the control. The rats were sacrificed at d₂, d₄, and d₇, 8 rats for each time point. Ulcer size was recorded every day. Thickness and proportion of new epithelium, inflammatory cell number in connective tissue, and collagen fiber content were analyzed. Results: At d₁, ulcer size showed good consistency within the same sides and between the bilateral sides (P=0.935). From d₂ to d₇, ulcer size was reduced (P<0.05) and collagen fiber content and thickness of new epithelium were increased persistently. Inflammatory cell number was increased from d₂ to d₄ and then decreased from d₄ to d₇ (P<0.05). Ulcer size was 16% to 37% smaller at MET side from d₂ to d₅ than that of control side (P<0.05), which was comparable bilaterally from d₆ to d₇. Inflammatory cell number was down regulated from d₁ to d₇ at MET side relative to that of control side (P<0.05). Collagen fiber content and thickness of new epithelium was upregulated at MET side from d₂ to d₄ compared with those at control side (P<0.05), which showed no difference bilaterally from d₄ to d₇. Conclusion: MET shows significant improving effect on OMU at early stages, which might relate to the inflammatory inhibition and reparative promotion

Key words: metformin, oral ulcer, histology , epithelium healing

梁兆佳, 贺嘉忻, 陈紫韵, 熊小琴, 霍昌宝, 林池灏, 刘晓明, 张君伟, 余挺. 二甲双胍对大鼠口腔黏膜溃疡的疗效之组织学评价[J]. 口腔医学研究, 2019, 35(7): 661-665.

LIANG Zhaojia, HE Jiaxin, CHEN Ziyun, XIONG Xiaoqin, HUO Changbao, LIN Chihao, LIU Xiaoming, ZHANG Junwei, YU Ting. Therapeutic Potentials of Metformin in Management of Oral Mucosal Ulcer in Rats: a Histological Study[J]. Journal of Oral Science Research, 2019, 35(7): 661-665.

参考文献

[1] Belenguerguallar I, Jiménezsoriano Y, Claramuntlozano A. Treatment of recurrent aphthous stomatitis. A literature review [J]. J Clin Exp Dent, 2014, 6(2):e168-e174.
[2] Cho CC, Chou RH, Yu C. Amlexanox blocks the interaction between S100A4 and epidermal growth factor and inhibits cell proliferation [J]. PLoS One, 2016, 11(8):e0161663.
[3] 王密,高莺,闫文婷,等.二甲双胍对骨质疏松大鼠晚期糖基化终产物影响的研究[J].口腔医学研究,2017,33(5):479-481.
[4] Ursini F, Russo E, Pellino G, et al. Metformin and autoimmunity: a “new deal” of an old drug [J]. Front Immunol, 2018, 9:1236.
[5] Bailey CJ. Metformin: historical overview [J]. Diabetologia, 2017, 60(9):1566-1576.
[6] Zhao P, Sui BD, Liu N, et al. Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application [J]. Aging Cell, 2017, 16(5):1083-1093.
[7] Pradeep AR, Patnaik K, Nagpal K, et al. Efficacy of 1% metformin gel in patients with moderate and severe chronic periodontitis: a randomized controlled clinical trial [J]. J Periodontol, 2017, 88(10):1023-1029.
[8] Ma J, Yu H, Liu J, et al. Metformin attenuates hyperalgesia and allodynia in rats with painful diabetic neuropathy induced by streptozotocin [J]. Eur J Pharmacol, 2015, 764(5):599-606.
[9] Wang X, Tang Y, Shen R, et al. Hepatocyte growth factor (HGF) optimizes oral traumatic ulcer healing of mice by reducing inflammation [J]. Cytokine, 2017, 99:275-280.
[10] Eming SA, Wynn TA, Martin P. Inflammation and metabolism in tissue repair and regeneration [J]. Science, 2017, 356(6342):1026-1030.
[11] Araújo AA, Pereira ASBF, Medeiros CACX, et al. Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis [J]. PLoS One, 2017, 12(8):e0183506.
[12] Ochoa-Gonzalez F, Cervantes-Villagrana AR, Fernandez-Ruiz JC, et al. Metformin induces cell cycle arrest, reduced proliferation, wound healing impairment in vivo and is associated to clinical outcomes in diabetic foot ulcer patients [J]. PLoS One, 2016, 11(3):e0150900.
[13] Karin M, Clevers H. Reparative inflammation takes charge of tissue regeneration [J]. Nature, 2016, 529(7586):307-315.
[14] Seelig E, Meyer S, Timper K, et al. Metformin prevents metabolic side effects during systemic glucocorticod treatment [J]. Eur J Endocrinol, 2017, 176(3):349-358.
[15] Takci Z, Karadag AS, Ertugrul DT, et al. Elevated insulin resistance in patients with recurrent aphthous stomatitis [J]. Clin Oral Investig, 2015, 19(6):1193-1197.
[16] 祁晶,余占海,刘燕,等.两种方法建立SD大鼠RAU模型的对比研究[J].实用口腔医学杂志,2011,27(2):185-189.

二甲双胍对大鼠口腔黏膜溃疡的疗效之组织学评价

Therapeutic Potentials of Metformin in Management of Oral Mucosal Ulcer in Rats: a Histological Study

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	朱肖雪, 赵苏峰, 杨旭东, 孙国文, 杨亚萍, 黄丽娟, 何凯. 计算机辅助设计联合3D打印应用于自体牙移植[J]. 口腔医学研究, 2021, 37(1): 76-80.
[2]	柳蓉蓉, 孟祥娇. 骨外型牙源性钙化上皮瘤1例[J]. 口腔医学研究, 2021, 37(1): 89-90.
[3]	程璐, 史剑杰. 骨膜减张技术在引导骨再生术中的应用研究进展[J]. 口腔医学研究, 2020, 36(9): 814-816.
[4]	王冬香, 王光素, 唐正龙, 陈友利, 高琼, 安宁. 下颌骨髁突高位骨折游离复位愈合过程中DKK-1/BMP-2的表达研究[J]. 口腔医学研究, 2020, 36(8): 748-752.
[5]	霍晓, 韩宁, 刘莉. 半导体激光治疗SD大鼠创伤性口腔溃疡的实验研究[J]. 口腔医学研究, 2020, 36(8): 770-775.
[6]	刘芳芳, 邱忠营, 王艳丽. EBV LMP1对牙龈上皮细胞促炎因子的调控及机制研究[J]. 口腔医学研究, 2020, 36(7): 654-657.
[7]	刘阳, 李善昌, 王长振, 周红梅, 董国福, 赵雪龙, 刘琦. 静磁场对大鼠下颌骨骨折愈合的研究[J]. 口腔医学研究, 2020, 36(6): 548-553.
[8]	余科, 贺晓萍, 文才, 刘旭琳, 杨健. IL-6抑制剂控制种植体愈合期炎症性骨吸收的动物实验研究[J]. 口腔医学研究, 2020, 36(3): 251-254.
[9]	张诗晨, 韩冰. 二甲双胍治疗头颈部鳞状细胞癌机制的研究进展[J]. 口腔医学研究, 2020, 36(12): 1091-1094.
[10]	梁德凤, 周鑫才, 吴芸菲. 二甲双胍调节PI3K/AKT通路对高糖诱导牙周膜成纤维细胞凋亡的影响研究[J]. 口腔医学研究, 2020, 36(12): 1103-1107.
[11]	程英杰, 高昕, 汪苑苑, 徐礼鲜, 顾宜, 王新文. 复方甘菊利多卡因对兔口腔溃疡愈合的影响及相关药理机制研究[J]. 口腔医学研究, 2020, 36(11): 1045-1049.
[12]	李德龙, 寇育荣, 葛弋民, 王泽琛, 赵腾飞, 宁春柳, 黄绍辉. 创伤性骨囊肿患者文献回顾研究——附15例病例分析[J]. 口腔医学研究, 2019, 35(8): 781-785.
[13]	刘艳玲, 赵曦, 余丽, 聂敏海. SOX-9在口腔鳞状细胞癌组织中的表达及其临床意义[J]. 口腔医学研究, 2019, 35(5): 439-442.
[14]	李勇伟,邱勋定,顾明,邓旎,谢莉莉. 同源形成素样蛋白2基因对口腔鳞状细胞癌侵袭、迁移及核因子-κB信号的影响[J]. 口腔医学研究, 2019, 35(2): 137-141.
[15]	王磊, 范亚伟. 口腔角化软组织缺损兔模型的建立与评估[J]. 口腔医学研究, 2018, 34(5): 567-571.