关键词: benzalkonium chloride (BAC) dry eye disease (DED) inflammation recombinant human thymosin β4 (rhTβ4)

Mesh : Animals Anti-Inflammatory Agents / adverse effects Benzalkonium Compounds / pharmacology Cytokines / therapeutic use Disease Models, Animal Dry Eye Syndromes / chemically induced drug therapy Humans Mice NF-kappa B Ophthalmic Solutions / adverse effects Quality of Life Thymosin

来  源:   DOI:10.3390/ijms23105458

Abstract:
Dry eye disease (DED) is a multifactorial ocular disorder that interferes with daily living and reduces quality of life. However, there is no most ideal therapeutic treatment to address all the deleterious defects of DED. The purpose of this study was to investigate the ability of recombinant human thymosin β4 (rhTβ4) to promote healing in a benzalkonium chloride (BAC)-induced mice DED model and the anti-inflammatory effects involved in that process. Eye drops consisting of 0.05% and 0.1% rhTβ4 were used for treatment of DED. Tear volume and corneal staining scores were measured after 7 days. Periodic acid-Schiff staining for gobleT cells in conjunctiva, immunohistochemical staining for CD4+ T cells, TUNEL assay for apoptotic positive cells in cornea and conjunctiva, qRT-PCR and ELISA assays for multiple cytokines were performed. All clinical parameters showed improvement in both the 0.05% and 0.1% rhTβ4 groups. Specifically, topical application of rhTβ4 significantly increased conjunctival gobleT cells and reduced apoptotic cells in conjunctiva. Mechanically, the rhTβ4 groups showed significantly reduced inflammatory cytokine levels and CD4+ T cells in conjunctiva by blocking NF-κB (nuclear factor kappa B) activation, suggesting that 0.05-0.1% rhTβ4 eye drops may be used as a potential therapeutic treatment for DED.
摘要:
干眼症(DED)是一种多因素的眼部疾病,会干扰日常生活并降低生活质量。然而,没有最理想的治疗方法来解决DED的所有有害缺陷。目的研究重组人胸腺素β4(rhTβ4)在苯扎氯铵(BAC)诱导的小鼠DED模型中促进愈合的能力以及参与该过程的抗炎作用。由0.05%和0.1%rhTβ4组成的滴眼剂用于治疗DED。7天后测量泪液体积和角膜染色评分。结膜中gobleT细胞的周期性酸性希夫染色,CD4+T细胞的免疫组织化学染色,TUNEL法检测角膜和结膜中的凋亡阳性细胞,进行多种细胞因子的qRT-PCR和ELISA测定。所有临床参数在0.05%和0.1%rhTβ4组中都显示出改善。具体来说,局部应用rhTβ4可显着增加结膜中的眼珠细胞,并减少结膜中的凋亡细胞。机械上,rhTβ4组通过阻断NF-κB(核因子κB)激活,显示结膜中炎症细胞因子水平和CD4+T细胞显著降低,提示0.05-0.1%rhTβ4滴眼液可作为DED的潜在治疗方法。
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