山东大学耳鼻喉眼学报 ›› 2017, Vol. 31 ›› Issue (4): 109-113.doi: 10.6040/j.issn.1673-3770.0.2016.420

• 荟萃分析 • 上一篇    下一篇

干眼动物模型研究进展

胡锦东,刘新泉   

  1. 上海中医药大学附属龙华医院眼科, 上海 200032
  • 收稿日期:2016-10-06 出版日期:2017-08-16 发布日期:2017-08-16
  • 通讯作者: 刘新泉. E-mail:drliuxinquan@hotmail.com
  • 基金资助:
    国家自然科学基金(81574028)

Research progress of dry eye animal model.

HU Jindong, LIU Xinquan   

  1. Department of Ophthalmology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
  • Received:2016-10-06 Online:2017-08-16 Published:2017-08-16

摘要: 干眼是临床最为常见的眼表疾病,其发病机制尚不清楚,建立有效的动物模型对于其机制的研究显得尤为重要。目前通过诱导动物自身免疫反应、摘除泪腺、阻断神经、使用副交感神经抑制药物等方法建立泪液生成不足型干眼动物模型;也可通过烧灼睑板腺、减少瞬目频率、喂养维生素A缺乏饲料、使用防腐剂、增加泪液渗透压、智能环境控制系统等方法建立蒸发过强型干眼动物模型;还可通过改变性激素水平、应用副交感神经抑制药物合并控制环境条件、摘除泪腺合并使用防腐剂等方法建立混合型干眼动物模型。就常见干眼动物模型作综述。

关键词: 干眼, 动物模型, 泪液分泌不足, 蒸发过强

Abstract: Dry eye is the most common ocular surface disease; however, its pathogenesis has not yet been fully elucidated. Therefore, the establishment of a dry eye model is particularly important for research into the conditions origins and its possible treatments. The current models used to establish tear deficiency either make use of an autoimmune reaction, involve the removal of the lacrimal gland(i.e., extirpation)or blockage of the lacrimal nerve, or use drugs that inhibit parasympathetic activity. Other methods of inducing dry eye involve burning the meibomian gland, decreasing the blink rate, reducing vitamin A intake, using preservatives, changing sex hormone levels, increasing tear osmolality, or carefully controlling the system environment. Meanwhile, some researchers combine the aforementioned models to produce dry eye, including combining parasympathetic inhibitory drugs with a controlled environmental system or using preservatives following removal of the lacrimal gland. In this article, we summarize the commonly used dry eye models.

Key words: Animal model, Tear deficiency, Dry eye, Evaporative

中图分类号: 

  • R77
[1] Lemp MA. The definition and classification of dry eye disease: report of the definition and classification subcommittee of the international dry eye workshop(2007)[J]. Ocul Surf, 2007, 5(2):75-92.
[2] Stern ME, Schaumburg CS, Pflugfelder SC. Dry eye as a mucosal autoimmune disease[J]. Int Rev Immunol, 2013, 32(1):19-41.
[3] Yagci A, Gurdal C. The role and treatment of inflammation in dry eye disease[J]. Int Ophthalmol, 2014, 34(6):1291-1301.
[4] Smith JA. The epidemiology of dry eye disease: report of the epidemiology subcommittee of the international dry eye workshop(2007)[J]. Ocul Surf, 2007, 5(2):93-107.
[5] Uchino M, Schaumberg DA.Dry eye disease: impact on quality of life and vision[J]. Curr Ophthalmol Rep, 2013, 1(2):51-57.
[6] 王贵渠, 赵琎, 徐海伟,等. C57BL/6.NOD-Aec1Aec2干燥综合征模型小鼠干眼表型及性别差异研究[J]. 第三军医大学学报, 2015, 37(9):876-880. WANG Guiqu, ZHAO Jin, XU Haiwei, et al. Gender difference in severity of dry eye phenotype in mouse model of Sj(o)gren's syndrome[J]. J Third Milit Med Univ, 2015, 37(9):876-880.
[7] Contreras-Ruiz L, Mir FA, Turpie B, et al. Sjögrens syndrome associated dry eye in a mouse model is ameliorated by topical application of integrin α4 antagonist GW559090[J]. Exp Eye Res, 2015, 143:1-8.
[8] 马晓昀, 何琳萍. SB203580对干燥综合征(SS)小鼠泪腺分泌功能的干预研究[J]. 复旦学报(医学版), 2012, 39(2):141-145. MA Xiaojun, HE Linping. The treatment effect of SB203580 on dry eye of Sjögrens syndrome(SS)mouse model[J]. Fudan Univ J Med Sci, 2012, 39(2):141-145.
[9] Marko CK, Menon BB, Chen G, et al. Spdef null mice lack conjunctival goblet cells and provide a model of dry eye[J]. Am J Pathol, 2013, 183(1):35-48.
[10] 杨丽媛, 边领斋, 李雪,等. 兔自身免疫性干眼模型的建立及泪腺炎症因子研究[J]. 眼科新进展, 2015, 35(9):810-815. YANG Liyuan, BIAN Lingzhai, LI Xue, et al. Establishment of rabbit autoimmune dry eye model and studies of lacrimal cytokines[J]. Recent Adv Ophthalmol, 2015, 35(9):810-815.
[11] 李淼, 张林. 大鼠泪液缺乏型干眼症眼表组织中IL- 6和TNF-α的表达[J]. 国际眼科杂志, 2010, 10(7):1281-1283. LI Miao, ZHANG Lin. IL- 6 and TNF-α expression in the ocular surface of aqueous tear deficiency dry eye-type rat[J]. Inter J Ophthalmol, 2010, 10(7):1281-1283.
[12] Joossen C, Lanckacker E, Zakaria N, et al. Optimization and validation of an existing, surgical and robust dry eye rat model for the evaluation of therapeutic compounds[J]. Exp Eye Res, 2016, 146:172-178.
[13] 施炜,李桥,王育良,等.反射缺乏型干眼动物模型的研究[J].中华实验眼科杂志,2009,27(4):296-299. SHI Wei, LI Qiao, WANG Yuliang, et al. Establishment of an animal model of dry eye due to lack of reflection[J]. Chin Ophthal Res, 2009, 27(4):296-299.
[14] Toshida H, Nguyen DH, Beuerman RW, et al. Evaluation of novel dry eye model: preganglionic parasympathetic denervation in rabbit.[J]. Invest Ophthalmol Vis Sci, 2007, 48(10):4468-4475.
[15] 施炜, 李桥, 王育良,等. 阿托品滴眼液制作兔干眼模型的研究[J]. 临床眼科杂志, 2011, 19(5):455-457. SHI Wei, LI Qiao, WANG Yuliang, et al. Establishment of a rabbit dry eye model by using sulfate atropine eye drops[J]. J Clin Ophthalmol, 2011, 19(5):455-457.
[16] 刘会娟, 黄悦, 张琰,等. 大鼠干眼模型的建立及其角膜神经的改变[J]. 眼科新进展, 2014, 34(5):422-427. LIU Huijuan, HUANG Yue, ZHANG Yan, et al. Establishment of rat dry eye model and changes of corneal nerve[J]. Recent Adv Ophthalmol, 2014, 34(5):422-427.
[17] 刘雪, 徐雯, 高卫萍. 硫酸阿托品滴眼液滴眼和氢溴酸东莨菪碱皮下注射制作水液缺乏型干眼兔模型实验研究[J]. 临床眼科杂志, 2015(3):263-266. LIU Xue, XU Wen, GAO Weiping. Research on the atropine sulfate eye drops and scopolamine hydrobromide subcutaneous injection production water lack of rabbit's dry eye model[J]. J Clin Ophthalmol, 2015(3):263-266.
[18] 朱海峰, 郝兆芹, 程钰,等. BTX-B诱导大鼠干眼模型的建立及评价标准[J]. 国际眼科杂志, 2015,15(9):1512-1515. ZHU Haifeng, HAO Zhaoqin, CHENG Yu, et al. Evaluation criterions and establishment of dry eye model of rats induced by BTX-B[J]. Inter Eye Sci, 2015, 15(9):1512-1515.
[19] 高伟, 程燕, 吴洁,等. 肉毒杆菌B诱导大鼠干眼模型中泪腺Lacritin蛋白表达的研究[J]. 眼科新进展, 2014, 34(1):21-24. GAO Wei, CHENG Yan, WU Jie, et al. Expression of Lacritin protein in lacrimal gland of rat dry eye model induced by botulinum toxin B[J]. Recent Adv Ophthalmol, 2014, 34(1):21-24.
[20] Kim DW, Lee SH, Ku SK, et al. Transduced PEP-1-FK506BP ameliorates corneal injury in botulinum toxin a-induced dry eye mouse model[J]. BMB Rep, 2013, 46(2):124-129.
[21] 王晓冬, 盛敏杰, 林安娟. 烧灼睑板腺开口并摘除第三眼睑制作兔睑板腺功能障碍性干眼模型的评价[J]. 中华实验眼科杂志, 2010, 28(9):827-831. WANG Xiaodong, SHENG Minjie, LIN Anjuan. Evaluation of establishing meibomian gland dysfunction dry eye model by cauterizing the meibomian gland orifices and excising the tertiary eyelid[J]. Chin Ophthal Res, 2010, 28(9):827-831.
[22] 韩臻, 郭滨, 任丛,等. 缝线法睑外翻手术建立兔干眼模型的实验研究[J]. 国际眼科杂志, 2012, 12(5):832-835. HAN Zhen, GUO Bin, REN Cong, et al. Experimental research of rabbit dry eye model by ectropion surgery[J]. Inter Eye Sci, 2012, 12(5):832-835.
[23] 刘盛春, 吴晓梅. 减少瞬目频率建立的蒸发过强型兔干眼模型[J]. 国际眼科杂志, 2009, 9(7):1265-1268. LIU Shengchun, WU Xiaomei. Rabbit model of evaporative dry eye established by decreasing blink rate[J]. Inter Eye Sci, 2009, 9(7):1265-1268.
[24] Li C, Song Y, Luan S, et al. Research on the stability of a rabbit dry eye model induced by topical application of the preservative benzalkonium chloride[J]. PloS One, 2012, 7(3):e33688.
[25] Kyung AK, Chung HL, Hoon JS, et al. The leaves of diospyros kaki exert beneficial effects on a benzalkonium chloride-induced murine dry eye model[J]. Mol Vis, 2016, 22:284-293.
[26] 马轶群, 杨青, 于海涛. 维生素A缺乏兔干眼病模型角膜上皮细胞凋亡及相关蛋白表达的关系[J]. 眼科新进展, 2008, 28(8):586-589. MA Yiqun, YANG Qing, YU Haitao. Apoptosis and related protein expression in vitamin A deficient rabbit cornea with experimental xerophthalmia[J]. Recent Adv Ophthalmol, 2008, 28(8):586-589.
[27] 刘超,耿燕. NFκBp65、NOS2在维生素A缺乏干眼模型兔角膜中的表达及意义[J].中华实验眼科杂志,2009,27(1):19-22. LIU Chao, GENG Yan. Expression and significance of NFκBp65 and NOS2 in cornea of experimental xerophthalmia rabbits[J]. Chin Ophthal Res, 2009, 27(1):19-22.
[28] 李晶,付川,谢汉平.高渗盐水点眼制作的小鼠干眼模型与评估[J].第三军医大学学报,2010,32(11):1183-1187. LI Jing, FU Chuan, XIE Hanping. Mouse model of dry eye induced by hyperosmolar saline and its evaluation[J]. Acta Acad Med Milit Tert, 2010, 32(11):1183-1187.
[29] Chen W, Zhang X, Zhang J, et al. A murine model of dry eye induced by an intelligently controlled environmental system.[J]. Invest Ophthalmol Vis Sci, 2008, 49(4):1386-1391.
[30] Zheng Q, Ren Y, Reinach PS, et al. Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye[J]. Exp Eye Res, 2014, 125:1-8.
[31] 黎黎,王双梅,郑璇,等.去势雄性小鼠泪膜功能异常及角膜上皮细胞超微结构改变[J].中华实验眼科杂志,2016,34(2):103-107. LI Li, WANG Shuangmei, ZHENG Xuan, et al. Dysfunction of tear film and ultrastructural changes of corneal epithelial cells in castrated male mice[J]. Chin J Exp Ophthalmol, 2016, 34(2):103-107.
[32] 彭玲,蔡伟浩,陆晓和,等.氟他胺诱导干眼模型大鼠角膜和泪腺组织病理变化及TNF-α、IL-1α的表达[J].眼科新进展,2016,36(6):506-511. PENG Ling, CAI Weihao, LU Xiaohe, et al. Pathological changes of cornea and lacrimal glands in dry eye rat model induced by flutamide and expression of TNF-α and IL-1α[J]. Recent Adv Ophthalmol, 2016, 36(6):506-511.
[33] 钟蕾,张晓峰,夏静,等.去卵巢大鼠结膜组织中炎性因子的表达变化及干眼相关检查的评估[J].中华实验眼科杂志,2014,32(9):807-812. ZHONG Lei, ZHANG Xiaofeng, XIA Jing, et al. Expression of inflammatory factors in conjunctiva and assessment of dry-eye associated examination in ovariectomized rat[J]. Chin J Exper Ophthalmol, 2014, 32(9):807-812.
[34] Rahimi Darabad R, Suzuki T, Richards SM, et al. Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?[J]. Exp Eye Res, 2014, 127:153-160.
[35] Simmons KT, Xiao Y, Pflugfelder SC, et al. Inflammatory Response to Lipopolysaccharide on the Ocular Surface in a Murine Dry Eye Model.[J]. Invest Ophthalmol Vis Sci, 2016, 57(6):2443-2451.
[36] Suwan-Apichon O, Rizen M, Rangsin R, et al. Botulinum toxin B-induced mouse model of keratoconjunctivitis sicca[J]. Invest Ophthalmol Vis Sci, 2006, 47(1):133-139.
[37] 陈淡嫦, 雷静, 赵澎,等. 胶原润眼液对新洁尔灭所致兔干眼症的治疗[J]. 眼科新进展, 2011, 31(11):1004-1007. CHEN Danchang, LEI Jing, ZHAO Peng, et al. Therapeutical effect of collagen eye drops on dry eye syndrome induced by benzalkonium bromide[J]. Recent Adv Ophthalmol, 2011, 31(11):1004-1007.
[1] 李凯,罗丹. 润目灵方激活LC3-ATG5自噬通路抑制炎症因子表达改善干眼大鼠眼表损伤的机制[J]. 山东大学耳鼻喉眼学报, 2026, 40(3): 92-101.
[2] 杨冠英,李元彬. 人工智能在干眼管理中的应用进展[J]. 山东大学耳鼻喉眼学报, 2026, 40(3): 115-120.
[3] 方璐, 雷玉丹, 王华. 环孢素滴眼液联合玻璃酸钠滴眼液治疗干眼临床效果的Meta分析[J]. 山东大学耳鼻喉眼学报, 2026, 40(2): 65-73.
[4] 宁煜赟,李彤,张馨心. 睑板腺功能障碍相关干眼的局部药物治疗[J]. 山东大学耳鼻喉眼学报, 2026, 40(2): 125-132.
[5] 李语辰,王旭. 巩膜镜治疗严重眼表疾病的有效性和安全性[J]. 山东大学耳鼻喉眼学报, 2026, 40(1): 149-154.
[6] 李志成,闫亚,戴梁平,应俊杰, 王仁忠. 嗅觉障碍小鼠和大鼠模型的研究进展[J]. 山东大学耳鼻喉眼学报, 2025, 39(2): 158-167.
[7] 毕赵静,李元彬. 睑板腺功能障碍实验模型及应用现状[J]. 山东大学耳鼻喉眼学报, 2024, 38(4): 159-165.
[8] 叶强,洛松巴宗,南苏亭,王浩,马进海,律鹏,张文芳. 色素上皮衍生因子与干眼的研究进展[J]. 山东大学耳鼻喉眼学报, 2024, 38(3): 151-156.
[9] 王佳慧,刘学勤. 全球近10年干眼相关生活质量研究——基于VOSviewer和CiteSpace的文献计量学及可视化分析[J]. 山东大学耳鼻喉眼学报, 2024, 38(2): 61-72.
[10] 段练,孟凡兰,党光福. 干眼对屈光性白内障手术的影响[J]. 山东大学耳鼻喉眼学报, 2022, 36(6): 1-6.
[11] 李彦松综述朱玉广审校. 泪膜稳定性对超声乳化术后视觉质量影响的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(6): 19-25.
[12] 白伶伶,王红星,王立春. 可吸收泪小管塞栓联合人工泪液治疗中重度干眼的有效性及对视觉相关生存质量的影响[J]. 山东大学耳鼻喉眼学报, 2022, 36(2): 78-82.
[13] 狄宇,李莹. 干眼炎症反应机制及抗炎治疗的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(2): 144-150.
[14] 黄天泽,陈迪,李莹. 机器学习在眼表疾病诊断及角膜手术中的应用进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(6): 13-19.
[15] 闫语,曾澳,何宇茜. 感染性角膜炎的模型制备[J]. 山东大学耳鼻喉眼学报, 2021, 35(5): 125-131.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!