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5% 来氟米特与生育酚联合滴眼液对小鼠干眼炎症和氧化应激的治疗潜力

Therapeutic Potential of Combined 5% Lifitegrast and Tocopherol Eye Drops in Managing Inflammation and Oxidative Stress in Murine Dry Eye.

作者信息

Moon Jayoung, Jiang Enying, Liu Jingting, Jin Hui, Yoon Hee Su, Choi Hoon-In, Choi Ji Suk, Qi Hong, Yoon Hyeon-Jeong, Yoon Kyung Chul

机构信息

Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea.

Department of Ophthalmology, Peking University Third Hospital, Beijing 100191, China.

出版信息

Pharmaceuticals (Basel). 2025 Jan 1;18(1):38. doi: 10.3390/ph18010038.

DOI:10.3390/ph18010038
PMID:39861101
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11769320/
Abstract

: This study aimed to evaluate the therapeutic effects of combined 5% lifitegrast (LF) and tocopherol (TCP) eye drops in a murine experimental dry eye (EDE) model. Female C57BL/6 were divided into seven groups: untreated controls, EDE control, EDE + 0.05% cyclosporin A (CsA), EDE + tocopherol (TCP), EDE + 5% LF, EDE + 5% LF + TCP (once daily), and EDE + 5% LF + TCP (twice daily). Clinical parameters (tear volume, tear break-up time (TBUT), corneal fluorescein staining score (CFSS), tear film lipid layer grade (TFLLG)) were assessed on days 7 and 14. Goblet cell density in the conjunctiva, CD4+ IFN-γ+ T cells, interleukin levels, reactive oxygen species (ROS) levels, and corneal apoptotic cells were analyzed on day 14. Monotherapy with 0.05% CsA and LF showed improvements in all clinical parameters compared to the EDE control ( < 0.05). Combination therapy groups demonstrated superior improvements in clinical parameters compared to the EDE control, 0.05% CsA, and 5% LF groups. CD4+ IFN-γ+ T cell percentages and ROS levels in the cornea and conjunctiva were markedly reduced in the combination groups compared with the 0.05% CsA and 5% LF groups ( < 0.01). Furthermore, corneal apoptotic cells significantly decreased in the combination groups compared to the 0.05% CsA and TCP groups ( < 0.05). Combined 5% LF and TCP eye drops improved tear film parameters and reduced inflammatory and oxidative stress markers. The combination therapy can mitigate ocular surface damage by managing inflammation and oxidative stress in dry eye.

摘要

本研究旨在评估5%利福平(LF)和生育酚(TCP)联合滴眼液对小鼠实验性干眼(EDE)模型的治疗效果。将雌性C57BL/6小鼠分为七组:未治疗对照组、EDE对照组、EDE + 0.05%环孢素A(CsA)组、EDE + 生育酚(TCP)组、EDE + 5% LF组、EDE + 5% LF + TCP(每日一次)组和EDE + 5% LF + TCP(每日两次)组。在第7天和第14天评估临床参数(泪液量、泪膜破裂时间(TBUT)、角膜荧光素染色评分(CFSS)、泪膜脂质层分级(TFLLG))。在第14天分析结膜杯状细胞密度、CD4+ IFN-γ+ T细胞、白细胞介素水平、活性氧(ROS)水平和角膜凋亡细胞。与EDE对照组相比,0.05% CsA和LF单药治疗在所有临床参数上均有改善(<0.05)。联合治疗组在临床参数方面的改善优于EDE对照组、0.05% CsA组和5% LF组。与0.05% CsA组和5% LF组相比,联合治疗组角膜和结膜中CD4+ IFN-γ+ T细胞百分比和ROS水平明显降低(<0.01)。此外,与0.05% CsA组和TCP组相比,联合治疗组角膜凋亡细胞明显减少(<0.05)。5% LF和TCP联合滴眼液改善了泪膜参数,降低了炎症和氧化应激标志物。联合治疗可通过控制干眼的炎症和氧化应激来减轻眼表损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/11769320/a3fbb636dac8/pharmaceuticals-18-00038-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/11769320/a3fbb636dac8/pharmaceuticals-18-00038-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/11769320/22c9410e3864/pharmaceuticals-18-00038-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/11769320/26b3e8d7f931/pharmaceuticals-18-00038-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/11769320/6509cfef2b57/pharmaceuticals-18-00038-g003.jpg
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本文引用的文献

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Antioxidants (Basel). 2024 Mar 29;13(4):422. doi: 10.3390/antiox13040422.
2
Lifitegrast Ophthalmic Solution 5% Is a Safe and Efficient Eyedrop for Dry Eye Disease: A Systematic Review and Meta-Analysis.5% 利非司特眼药水是一种治疗干眼病安全有效的眼药水:一项系统评价与荟萃分析
J Clin Med. 2022 Aug 26;11(17):5014. doi: 10.3390/jcm11175014.
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The global prevalence of dry eye disease: A Bayesian view.干眼症的全球患病率:贝叶斯视角。
Ophthalmic Physiol Opt. 2021 Nov;41(6):1254-1266. doi: 10.1111/opo.12888. Epub 2021 Sep 21.
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Effects of eye drops containing a mixture of 3% diquafosol sodium and tocopherol acetate (vitamin E) on the ocular surface of murine dry eye.含有3%双醋瑞因钠和醋酸生育酚(维生素E)混合物的滴眼液对小鼠干眼眼表的影响。
Cutan Ocul Toxicol. 2021 Dec;40(4):350-358. doi: 10.1080/15569527.2021.1973022. Epub 2021 Sep 8.
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Effects of extracts on human corneal epithelial cells and experimental dry eye.提取物对人角膜上皮细胞及实验性干眼的影响。
Exp Ther Med. 2020 Aug;20(2):1607-1615. doi: 10.3892/etm.2020.8830. Epub 2020 Jun 3.
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Physician Satisfaction with Anti-Inflammatory Topical Medications for the Treatment of Dry Eye Disease.医生对用于治疗干眼病的抗炎局部用药的满意度
Clin Ophthalmol. 2020 Mar 25;14:931-938. doi: 10.2147/OPTH.S237832. eCollection 2020.
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Clin Ophthalmol. 2020 Mar 19;14:875-883. doi: 10.2147/OPTH.S233194. eCollection 2020.
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