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重组人胸腺素 β4(rhTβ4)调节抗炎反应以缓解苯扎氯铵(BAC)诱导的干眼症。

Recombinant Human Thymosin β4 (rhTβ4) Modulates the Anti-Inflammatory Responses to Alleviate Benzalkonium Chloride (BAC)-Induced Dry Eye Disease.

机构信息

Beijing Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China.

Eye Institute of Xiamen University & Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen 361104, China.

出版信息

Int J Mol Sci. 2022 May 13;23(10):5458. doi: 10.3390/ijms23105458.

DOI:10.3390/ijms23105458
PMID:35628276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9141377/
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)是一种多因素的眼疾,会干扰日常生活并降低生活质量。然而,目前还没有最理想的治疗方法来解决 DED 的所有有害缺陷。本研究旨在探讨重组人胸腺素β4(rhTβ4)在苯扎氯铵(BAC)诱导的小鼠 DED 模型中促进愈合的能力,以及其涉及的抗炎作用。使用含有 0.05%和 0.1%rhTβ4 的眼药水治疗 DED。治疗 7 天后测量泪液体积和角膜染色评分。对结膜进行过碘酸希夫(PAS)染色以检测 goblet 细胞,对 CD4 T 细胞进行免疫组织化学染色,对角膜和结膜中的凋亡阳性细胞进行 TUNEL 检测,对多种细胞因子进行 qRT-PCR 和 ELISA 检测。所有临床参数在 0.05%和 0.1%rhTβ4 组均有改善。具体来说,rhTβ4 局部应用可显著增加结膜 goblet 细胞,并减少结膜中的凋亡细胞。通过阻断 NF-κB(核因子 kappa B)激活,rhTβ4 组显示出明显降低的结膜中炎症细胞因子水平和 CD4 T 细胞,表明 0.05%-0.1%rhTβ4 眼药水可能可作为 DED 的潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/9141377/412d7d92f98a/ijms-23-05458-g005.jpg
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