Effects of the pirfenidone eye drops for rat corneal scarring after acute alkali burn

doi:10.12092/j.issn.1009-2501.2018.08.007

Abstract

Abstract:

AIM: To study the efficacy of pirfenidone on corneal scarring after acute alkali burn in rat model. METHODS: Thirty adult healthy SD rats were random selected for the experiment. Ten rats were used as control group. Twenty rats were used to make acute alkali burn model on the left eye, and divided into PFD and PBS group(10 rats each group) after successful modeling. The PFD group was treated with pirfenidone eye drops (3 mg/mL), and PBS group was treated with phosphate buffered saline, the treatments of the left eye were administered 4 times daily and continued for 14 days. At 14 d post-therapy, the corneal haze was analyzed by slit lamp microscope, and then all rats were killed and their left cornea was removed. HE staining was used to observe all groups of the structure of the corneal tissue. The presences of blood vessels in the corneal tissue were observed by immunohistochemical CD34 staining. The expressions of TGF-β1 protein in the cornea were examined by Western blot. RESULTS: The score of corneal haze in PFD group (0.30±0.48) was significantly lower than that in PBS group (3.40±0.52, P<0.05). HE staining showed that there were many inflammatory cell infiltrations and proliferation of fibrous tissue in the corneal tissue of PBS group, while the morphology and structure of corneal tissues in the PFD group had no significant pathological changes. PFD group showed lower microvessel quantity than the PBS group. PFD group down-regulated TGF-β1 protein expression as compared with PBS group. CONCLUSION: PFD can significantly inhibit corneal scarring after acute alkali burn in rat model by down-regulating TGF-β1 expression and inhibiting the corneal neovascularization.

Key words: pirfenidone, cornea, alkali burn, scarring

CLC Number:

R965.2

ZOU Zhikang, WU Gongfa, QIU Lizhen, LIU Yujun, HUANG Qiting, ZENG Yuting. Effects of the pirfenidone eye drops for rat corneal scarring after acute alkali burn[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(8): 881-885.

References

［1］王朋, 吴志鸿. 角膜碱烧伤的药物治疗研究进展［J］. 中国急救复苏与灾害医学杂志, 2016, 11(7): 735-738.
［2］George PM, Wells AU. Pirfenidone for the treatment of idiopathic pulmonary fibrosis［J］. Expert Rev Clin Pharmacol, 2017, 10(5): 483-491.
［3］付麟紫, 吴晓梅. 特发性肺纤维化药物治疗推荐［J］. 中华老年多器官疾病杂志, 2017, 16(3): 234-237.
［4］陈钰清, 闫永吉, 仇美华, 等. 吡非尼酮治疗肺纤维化的疗效与安全性meta分析［J］. 临床药物治疗杂志, 2016, 14(4): 13-22.
［5］Wilson SE. Corneal myofibroblast biology and pathobiology: generation, persistence, and transparency［J］. Exp Eye Res, 2012, 99(1): 78-88.
［6］陈俊杰, 吴共发, 林俊汕, 等. 吡非尼酮对大鼠角膜基质细胞增殖的影响［J］. 国际眼科杂志, 2015, 15 (2): 201-204.
［7］吴共发, 邱丽浈, 曾宇婷, 等. 自制吡非尼酮滴眼液局部应用于角膜的安全性研究［J］. 中华眼科医学杂志（电子版）, 2017, 7(6): 250-256.
［8］白军强,赵世红,秦海峰,等.枸橼酸-磷酸氢二钠缓冲液冲洗对小鼠急性角膜化学伤眼表的保护作用［J］.中华实验眼科杂志,2017,35(2):122-127.
［9］Li C, Han R, Kang L, et al. Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-α in myocardial infarction-induced cardiac fibrosis［J］. Sci Rep, 2017, 7: 40523.
［10］Seniutkin O, Furuya S, Luo YS, et al. Effects of pirfenidone in acute and sub-chronic liver fibrosis, and an initiation-promotion cancer model in the mouse［J］. Toxicol Appl Pharmacol, 2018, 339: 1-9.
［11］Li Z, Liu X, Wang B, et al. Pirfenidone suppresses MAPK signalling pathway to reverse epithelial-mesenchymal transition and renal fibrosis［J］. Nephrology (Carlton), 2017, 22(8): 589-597.
［12］陈钰清, 闫永吉, 仇美华, 等. 吡非尼酮抗纤维化作用的研究进展［J］. 临床药物治疗组杂志, 2016, 14(5): 1-7.
［13］李亨辉, 李云端, 邵毅, 等. 吡非尼酮滴眼液在兔眼青光眼手术中的应用研究［J］. 中国实用眼科杂志, 2015, 33(10): 1179-1184.
［14］Chowdhury S, Guha R, Trivedi R, et al. Pirfenidone nanoparticles improve corneal wound healing and prevent scarring following alkali burn［J］. PLoS One, 2013 , 8(8): e70528.
［15］Fink MK,Giuliano EA,Tandon A,et al.Therapeutic potential of Pirfenidone for treating equine corneal scarring［J］.Vet Ophthalmol,2015,18(3):242-250.
［16］Gibson DJ, Schultz GS. A corneal scarring model［J］. Methods Mol Biol, 2013, 1037: 277-298.
［17］Tandon A, Tovey JC, Sharma A, et al. Role of transforming growth factor beta in corneal function, biology, and pathology［J］. Curr Mol Med, 2010, 10: 565-578.
［18］张露,李霞. TGF-β在角膜损伤修复中的时间和空间分布［J］. 眼科新进展, 2017, 37(2): 184-188.
［19］Ljubimov AV, Saghizadeh M. Progress in corneal wound healing ［J］. Prog Retin Eye Res, 2015, 49(6): 17-45.
［20］刘晓坤, 赵平. 角膜新生血管的发病机制［J］. 眼科新进展, 2006, 26(3): 230-233.

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[3]	TENG Yi, YANG Hai-ling. Research progress on the pharmacokinetic profile of borneol [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(4): 469-475.
[4]	ZHAO Shi-Hong, GUO Lian-Zheng, HOU Qin-Ying, WANG Kai-Hui. The preparation of corneal collagen shield and its clinical application [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 1998, 3(4): 282-284.