Abstract

Objective

To elucidate the implications of L-carnosine on interleukin-1α (IL-1α)-induced inflammation of lacrimal glands (LGs).

Materials and methods

Forty rabbits were divided equally into four groups: control group (G1), IL-1α (G2), L-carnosine (G3), and L-carnosine plus IL-1α (G4). Several clinical, histopathological, immunohistochemical, morphometric, and biochemical investigations were performed, followed by statistical analysis to diagnose the presence of dry eye disease (DED).

Results

The LGs of G2 rabbits showed degeneration of the acinar cells, increased deposition of collagen fibers, and marked immunoexpression of FasL; elevated levels of interferon-γ, tumor necrosis factor-α, transforming growth factor-β1, and malondialdehyde; and decreased levels of glutathione peroxidase, superoxide dismutase, catalase, and reactive oxygen species compared with those of G1 rabbits. In contrast, administration of L-carnosine to G4 rabbits revealed marked improvement of all previously harmful changes in G2 rabbits, indicating the cytoprotective effects of L-carnosine against IL-1α-induced inflammation of LGs.

Conclusions

IL-1α induced inflammation of LGs and eye dryness via oxidative stress, proinflammatory, apoptotic, and profibrotic effects, whereas L-carnosine mitigated DED through antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic effects on LGs. Therefore, this work demonstrates for the first time that L-carnosine may be used as adjuvant therapy for the preservation of visual integrity in patients with DED.

• Highlights

• IL-1α induced dry eye disease through its oxidative stress, proinflammatory, apoptotic and profibrotic effects on the lacrimal glands of rabbit.

• L-carnosine has antioxidant, anti-inflammatory, antiapoptotic and antifibrotic effects.

• L-carnosine mitigated IL-1α induced dry eye disease via elevating the levels of FasL, IFN-γ, TNF-α, TGFβ1 and MDA as well as reducing the levels of antioxidants (GPx, SOD, and catalase) and ROS in the lacrimal glands of rabbit.

• L-carnosine could be used as a novel adjuvant therapy for the treatment of dry eye disease.

中文翻译：

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L-肌肽通过其抗氧化、抗炎、抗凋亡和抗纤维化作用减轻白细胞介素-1α诱导的兔干眼病

摘要

客观的

阐明 L-肌肽对白细胞介素 1α (IL-1α) 诱导的泪腺 (LG) 炎症的影响。

材料和方法

四十只兔子平均分为四组：对照组（G1）、IL-1α（G2）、L-肌肽（G3）和L-肌肽加IL-1α（G4）。进行了几项临床、组织病理学、免疫组织化学、形态计量学和生化研究，然后进行统计分析以诊断干眼病 (DED) 的存在。

结果

G2兔LGs腺泡细胞变性，胶原纤维沉积增多，FasL免疫表达明显；干扰素-γ、肿瘤坏死因子-α、转化生长因子-β1和丙二醛水平升高；与 G1 兔相比，谷胱甘肽过氧化物酶、超氧化物歧化酶、过氧化氢酶和活性氧的水平降低。相比之下，向 G4 兔施用 L-肌肽显示 G2 兔所有先前有害变化的显着改善，表明 L-肌肽对 IL-1α 诱导的 LG 炎症的细胞保护作用。

结论

IL-1α 通过氧化应激、促炎、凋亡和促纤维化作用诱导 LG 炎症和眼干，而 L-肌肽通过对 LG 的抗氧化、抗炎、抗凋亡和抗纤维化作用减轻 DED。因此，这项工作首次证明 L-肌肽可用作维持 DED 患者视觉完整性的辅助治疗。

• 强调

• IL-1α通过其对兔泪腺的氧化应激、促炎、凋亡和促纤维化作用诱导干眼症。

• L-肌肽具有抗氧化、抗炎、抗凋亡和抗纤维化作用。

• L-肌肽通过提高 FasL、IFN-γ、TNF-α、TGFβ1 和 MDA 的水平以及降低泪腺中抗氧化剂（GPx、SOD 和过氧化氢酶）和 ROS 的水平来减轻 IL-1α 诱导的干眼症兔的腺体。

• L-肌肽可用作治疗干眼病的新型辅助疗法。