Lipoxin A4 (LXA4) Reduces Alkali-Induced Corneal Inflammation and Neovascularization and Upregulates a Repair Transcriptome.
Lipoxin A4 (LXA4) Reduces Alkali-Induced Corneal Inflammation and Neovascularization and Upregulates a Repair Transcriptome.
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Lipoxin A4（LXA4）减少了碱诱导的角膜炎症和新血管形成，并上调了修复转录组。
DOI：
10.3390/biom13050831
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发表时间：
2023-05-13
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
目的：探讨生物活性脂质介质LXA 4对严重角膜碱损伤大鼠模型的抗炎和抗血管生成作用。方法：采用麻醉的Sprague道利大鼠，造成右眼角膜碱损伤。将浸泡在1 N NaOH中的Φ 4 mm滤纸盘置于角膜中心，使其受伤。损伤后，用LXA 4（65 ng/20 μL）或溶剂局部处理大鼠，每天三次，持续14天。记录角膜混浊、新生血管（NV）和前房出血，并以盲法进行评价。通过RNA测序和毛细管Western印迹分析参与山茱萸修复的促炎细胞因子表达和基因。通过免疫荧光和流式细胞术分析角膜细胞浸润和从血液中分离的单核细胞。结果：与溶媒治疗相比，LXA 4局部治疗两周显著降低了角膜混浊、NV和前房出血。RNA-seq和Western blot结果显示，LXA 4降低促炎细胞因子白细胞介素（IL）-1β和IL-6以及促血管生成介质基质金属蛋白酶（MMP）-9和VEGFA的基因和蛋白表达。它还诱导参与角化和ErbB信号传导的基因，并下调免疫途径以刺激伤口愈合。流式细胞术和免疫组织化学显示，与媒介物处理相比，用LXA 4处理的角膜中的嗜中性粒细胞浸润显著更少。它还显示，与血液分离的单核细胞中的M1相比，LXA 4处理增加了2型巨噬细胞（M2）的比例。结论：LXA 4可减轻碱烧伤引起的角膜炎症和新生血管形成。其作用机制包括抑制炎性白细胞浸润，减少细胞因子释放，抑制血管生成因子，促进角膜修复基因表达和碱烧伤角膜血液中巨噬细胞极化。LXA 4有可能作为严重角膜化学损伤的治疗候选者。
Purpose: To investigate the anti-inflammatory and anti-angiogenic effects of the bioactive lipid mediator LXA4 on a rat model of severe corneal alkali injury. Methods: To induce a corneal alkali injury in the right eyes of anesthetized Sprague Dawley rats. They were injured with a Φ 4 mm filter paper disc soaked in 1 N NaOH placed on the center of the cornea. After injury, the rats were treated topically with LXA4 (65 ng/20 μL) or vehicle three times a day for 14 days. Corneal opacity, neovascularization (NV), and hyphema were recorded and evaluated in a blind manner. Pro-inflammatory cytokine expression and genes involved in cornel repair were assayed by RNA sequencing and capillary Western blot. Cornea cell infiltration and monocytes isolated from the blood were analyzed by immunofluorescence and by flow cytometry. Results: Topical treatment with LXA4 for two weeks significantly reduced corneal opacity, NV, and hyphema compared to the vehicle treatment. RNA-seq and Western blot results showed that LXA4 decreased the gene and protein expression of pro-inflammatory cytokines interleukin (IL)-1β and IL-6 and pro-angiogenic mediators matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGFA). It also induces genes involved in keratinization and ErbB signaling and downregulates immune pathways to stimulate wound healing. Flow cytometry and immunohistochemistry showed significantly less infiltration of neutrophils in the corneas treated with LXA4 compared to vehicle treatment. It also revealed that LXA4 treatment increases the proportion of type 2 macrophages (M2) compared to M1 in blood-isolated monocytes. Conclusions: LXA4 decreases corneal inflammation and NV induced by a strong alkali burn. Its mechanism of action includes inhibition of inflammatory leukocyte infiltration, reduction in cytokine release, suppression of angiogenic factors, and promotion of corneal repair gene expression and macrophage polarization in blood from alkali burn corneas. LXA4 has potential as a therapeutic candidate for severe corneal chemical injuries.
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影响因子：
3.4
作者：
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通讯作者：
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