干眼症动物模型和药效评价研究进展
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摘要
干眼症是一种局部或全身多因素引起的泪腺低分泌而导致泪膜异常、眼表上皮干变的常见眼科疾病。开发治疗干眼症新药是眼科药物开发的热点。本文综述了干眼症的实验动物模型和药效评价指标的研究进展,旨在为治疗干眼症新药非临床有效性研究提供思路。
Xerophthalmia is a common ophthalmic disease caused by low secretion of lacrimal glands caused by local or systemic factors, resulting in abnormal tear film and dry eye epithelium. The development of new drugs for dry eye is a hot spot in the development of ophthalmic drugs. In this paper, the research progress in experimental animal model and efficacy evaluation index of dry eye is reviewed to provide some ideas for the non-clinical efficacy of the new drugs for xerophthalmia.
Xerophthalmia is a common ophthalmic disease caused by low secretion of lacrimal glands caused by local or systemic factors, resulting in abnormal tear film and dry eye epithelium. The development of new drugs for dry eye is a hot spot in the development of ophthalmic drugs. In this paper, the research progress in experimental animal model and efficacy evaluation index of dry eye is reviewed to provide some ideas for the non-clinical efficacy of the new drugs for xerophthalmia.
引文
[1]Cifuentes M,Del PB,Verakellet C. Pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia of Sj?gren’s Syndrome:A double blind control trial[J].Brit J Dermatol,2018,22(1):8697-9245.
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[3]Vishwanath S,Everett S,Shen L,et al. Xerophthalmia of Sjogren’s syndrome diagnosed with anti-salivary gland protein 1 antibodies[J]. Case Reports in Ophthalmology,2014,5(2):186-189.
[4]褚晨晨,茹玉莎,张琰,等.干眼新型干预手段的研究进展及其对眼表微环境的保护作用机制[J].国际眼科纵览,2017,41(6):274-281.
[5]Wu SQ,Dai Q,Xu JL,et al. Combined effect of traditional Chinese and Western medicine on inflammatory factors in patients with diabetes-induced xerophthalmia[J].Genet Mol Res,2016,15(4):150-158.
[6]杨燕宁,朱伽月,宋秀胜,等.环孢素A临床应用的研究进展[J].国际眼科杂志,2017,17(3):463-466.
[7]李凯,王育良,张传伟.鬼针草治疗阿托品干眼兔模型的实验研究[J].西部中医药,2017,30(2):13-15.
[8]BucoloC,Fidilio A,CbmP,etal. Antioxidantand osmoprotecting activity of taurine in dry eye models[J]. J Ocul Pharmacol Ther,2017,34(3):1-7.
[9]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.
[10]杨延婷,张丹,吴丽洁,等.东莨菪碱与苯扎氯铵干眼症大鼠造模方法研究[J].动物医学进展,2017,38(10):43-50.
[11]谢阳金,左韬.杞参膏对干眼症SD大鼠血清Mig、IP-10影响随机平行对照研究[J].实用中医内科杂志,2017,31(6):46-49.
[12]杜娟,李志辉,赵奋图,等.羊膜提取液治疗兔干眼症的实验研究[J].国际眼科杂志,2016,16(7):1232-1236.
[13]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(2):284-293.
[14]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.
[15]李晶.一种新的干眼病模型——高渗盐水点眼小鼠干眼病模型的建立与评估[D].重庆:第三军医大学,2010.
[16]谢阳金,左韬.杞参膏对干眼症模型大鼠泪液分泌及血清I-TAC含量的影响[J].中医药临床杂志,2017,29(6):859-862.
[17]曹雪艳,丁亚南.养阴生津中药熏蒸联合人工泪液治疗蒸发过强型干眼的效果分析[J].北方药学,2018,15(6):177-188.
[18]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.
[19]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.
[20]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.
[21]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(39):172-178.
[22]Toshida H,Nguyen DH,Beuerman RW,et al. Evaluation of novel dry eye model:preganglionic parasympa thetic denervation in rabbit[J]. Invest Ophthalmol Vis Sci,2007,48(10):4468-4475.
[23]王超,丁文涛,于颖梅,等.远端取穴与眼周取穴治疗干眼症疗效对比观察[J].中国针灸,2017,37(10):1069-1072.
[24]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.
[25]Hos D,Cursiefen C. Severe vitamin A deficiency in a child presenting as xerophthalmia[J]. J Pediatr,2014,165(4):875-883.
[26]Chiu M,Dillon A. Vitamin A deficiency and xerophthalmia in children of a developed country[J]. J Paediatr Child Health,2016,52(7):699-703.
[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.
[28]黎黎,郑璇,王双梅,等.雄激素调节小鼠泪膜功能与角膜上皮细胞Mucins表达的体内研究[J].国际眼科杂志,2016,16(7):1228-1231.
[29]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.
[30]刘宇,盛敏杰,李冰,等. MRL/lpr小鼠干眼模型的实验研究[J].同济大学学报(医学版),2017,38(5):24-27.
[31]刘宇,盛敏杰,林安娟,等. PPARγ配体盐酸吡格列酮对MRL/lpr小鼠泪腺炎症干预的研究[J].同济大学学报(医学版),2013,34(1):8-12.
[32]Zheng Q,Ren Y,Reinach PS,et al. Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye[J]. Exp Eye Res,2014,12(5):1-8.
[33]Wu SQ,Dai Q,Xu JL,et al. Combined effect of traditional Chinese and Western medicine on inflammatory factors in patients with diabetes-induced xerophthalmia[J].Genet Mol Res Gmr,2016,15(4):15-17.
[34]熊翠菊.局部滴用洁尔灭防腐剂建立兔干眼模型[D].广州:中山大学,2007.
[35]程丽萍,胡美君.干眼症与慢性结膜炎的误诊分析[J].中华现代眼耳鼻喉科杂志,2008,5(4):338-340.
[36]刘莉,何慧琴.干眼动物模型制作的研究进展[J].长春中医药大学学报,2012,28(5):922-924.
[37]詹远,胡馨月,刘松青.环孢素A治疗干眼疗效和安全性系统评价[J].中国药业,2018,27(3):47-51.
[38]Kang SW,Kim KA,Lee CH,et al. A standardized extract of Rhynchosia volubilis Lour. exerts a protective effect on benzalkonium chloride-induced mouse dry eye model[J].J Ethnopharmacol,2017,215(7):91-100.
[39]刘会娟.α-黑素细胞刺激素对东莨菪碱诱导的大鼠干眼眼表的保护作用[D].天津:天津医科大学,2014.
[40]Traipe-salas F,Traipecastro L,Salinastoro D,et al.Progress in tear microdesiccate analysis by combining various transmitted-light microscope techniques[J]. Biol Res,2016,49(1):28-38.
[2]陈静.干眼症常见病因及护理研究进展[J].医学信息,2017,30(6):28-29.
[3]Vishwanath S,Everett S,Shen L,et al. Xerophthalmia of Sjogren’s syndrome diagnosed with anti-salivary gland protein 1 antibodies[J]. Case Reports in Ophthalmology,2014,5(2):186-189.
[4]褚晨晨,茹玉莎,张琰,等.干眼新型干预手段的研究进展及其对眼表微环境的保护作用机制[J].国际眼科纵览,2017,41(6):274-281.
[5]Wu SQ,Dai Q,Xu JL,et al. Combined effect of traditional Chinese and Western medicine on inflammatory factors in patients with diabetes-induced xerophthalmia[J].Genet Mol Res,2016,15(4):150-158.
[6]杨燕宁,朱伽月,宋秀胜,等.环孢素A临床应用的研究进展[J].国际眼科杂志,2017,17(3):463-466.
[7]李凯,王育良,张传伟.鬼针草治疗阿托品干眼兔模型的实验研究[J].西部中医药,2017,30(2):13-15.
[8]BucoloC,Fidilio A,CbmP,etal. Antioxidantand osmoprotecting activity of taurine in dry eye models[J]. J Ocul Pharmacol Ther,2017,34(3):1-7.
[9]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.
[10]杨延婷,张丹,吴丽洁,等.东莨菪碱与苯扎氯铵干眼症大鼠造模方法研究[J].动物医学进展,2017,38(10):43-50.
[11]谢阳金,左韬.杞参膏对干眼症SD大鼠血清Mig、IP-10影响随机平行对照研究[J].实用中医内科杂志,2017,31(6):46-49.
[12]杜娟,李志辉,赵奋图,等.羊膜提取液治疗兔干眼症的实验研究[J].国际眼科杂志,2016,16(7):1232-1236.
[13]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(2):284-293.
[14]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.
[15]李晶.一种新的干眼病模型——高渗盐水点眼小鼠干眼病模型的建立与评估[D].重庆:第三军医大学,2010.
[16]谢阳金,左韬.杞参膏对干眼症模型大鼠泪液分泌及血清I-TAC含量的影响[J].中医药临床杂志,2017,29(6):859-862.
[17]曹雪艳,丁亚南.养阴生津中药熏蒸联合人工泪液治疗蒸发过强型干眼的效果分析[J].北方药学,2018,15(6):177-188.
[18]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.
[19]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.
[20]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.
[21]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(39):172-178.
[22]Toshida H,Nguyen DH,Beuerman RW,et al. Evaluation of novel dry eye model:preganglionic parasympa thetic denervation in rabbit[J]. Invest Ophthalmol Vis Sci,2007,48(10):4468-4475.
[23]王超,丁文涛,于颖梅,等.远端取穴与眼周取穴治疗干眼症疗效对比观察[J].中国针灸,2017,37(10):1069-1072.
[24]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.
[25]Hos D,Cursiefen C. Severe vitamin A deficiency in a child presenting as xerophthalmia[J]. J Pediatr,2014,165(4):875-883.
[26]Chiu M,Dillon A. Vitamin A deficiency and xerophthalmia in children of a developed country[J]. J Paediatr Child Health,2016,52(7):699-703.
[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.
[28]黎黎,郑璇,王双梅,等.雄激素调节小鼠泪膜功能与角膜上皮细胞Mucins表达的体内研究[J].国际眼科杂志,2016,16(7):1228-1231.
[29]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.
[30]刘宇,盛敏杰,李冰,等. MRL/lpr小鼠干眼模型的实验研究[J].同济大学学报(医学版),2017,38(5):24-27.
[31]刘宇,盛敏杰,林安娟,等. PPARγ配体盐酸吡格列酮对MRL/lpr小鼠泪腺炎症干预的研究[J].同济大学学报(医学版),2013,34(1):8-12.
[32]Zheng Q,Ren Y,Reinach PS,et al. Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye[J]. Exp Eye Res,2014,12(5):1-8.
[33]Wu SQ,Dai Q,Xu JL,et al. Combined effect of traditional Chinese and Western medicine on inflammatory factors in patients with diabetes-induced xerophthalmia[J].Genet Mol Res Gmr,2016,15(4):15-17.
[34]熊翠菊.局部滴用洁尔灭防腐剂建立兔干眼模型[D].广州:中山大学,2007.
[35]程丽萍,胡美君.干眼症与慢性结膜炎的误诊分析[J].中华现代眼耳鼻喉科杂志,2008,5(4):338-340.
[36]刘莉,何慧琴.干眼动物模型制作的研究进展[J].长春中医药大学学报,2012,28(5):922-924.
[37]詹远,胡馨月,刘松青.环孢素A治疗干眼疗效和安全性系统评价[J].中国药业,2018,27(3):47-51.
[38]Kang SW,Kim KA,Lee CH,et al. A standardized extract of Rhynchosia volubilis Lour. exerts a protective effect on benzalkonium chloride-induced mouse dry eye model[J].J Ethnopharmacol,2017,215(7):91-100.
[39]刘会娟.α-黑素细胞刺激素对东莨菪碱诱导的大鼠干眼眼表的保护作用[D].天津:天津医科大学,2014.
[40]Traipe-salas F,Traipecastro L,Salinastoro D,et al.Progress in tear microdesiccate analysis by combining various transmitted-light microscope techniques[J]. Biol Res,2016,49(1):28-38.