氯沙坦对皮肤伤口愈合的调节：关注MCP-1活性和胶原合成

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-12 DOI:10.1016/j.tice.2025.103079

Mohammad Kazempour , Mohammad Hashemnia , Zahra Nikousefat , Behdad Beheshti Alagha

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引用次数: 0

摘要

氯沙坦是一种选择性血管紧张素II型1受体（AT1R）拮抗剂，具有抗炎和抗纤维化特性，局部应用时可加速伤口愈合。伤口愈合受损仍然是一个全球卫生问题，导致慢性伤口、感染和过度疤痕。这项研究首次评估了局部应用氯沙坦的伤口愈合潜力。主要方法Sprague-Dawley大鼠全层切除创面，外用氯沙坦（5 %或10 %）、底霜或不处理。在伤后10、20和30天进行宏观和组织学评估。除了分析髓过氧化物酶（MPO）、单核细胞趋化蛋白-1 （MCP-1）、糖胺聚糖（GAGs）和羟脯氨酸外，还评估了伤口愈合率、胶原纤维排列、血运重建和炎症细胞浸润等其他参数。主要发现：沙坦治疗的伤口愈合明显加快，细胞角蛋白14 （CK14）增强，上皮再生改善，炎症浸润减少。MPO活性明显下降，特别是在早期愈合，MCP-1调节跟随巨噬细胞动力学。组织学结果显示成纤维细胞成熟、血运重建和有组织的胶原沉积增强。羟脯氨酸和GAGs水平升高证实细胞外基质形成改善。本研究首次证实了局部应用氯沙坦通过调节炎症、增强基质重塑和调节CK14表达促进创面愈合的疗效。这些发现支持氯沙坦作为一种新的局部药物的治疗重新定位，并为其在慢性伤口治疗中的临床发展铺平了道路，包括糖尿病和缺血性溃疡。

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Modulation of cutaneous wound healing by Losartan: A focus on MCP-1 activity and collagen synthesis

Losartan, a selective angiotensin II type 1 receptor (AT1R) antagonist, has shown anti-inflammatory and anti-fibrotic properties that may accelerate wound healing when applied topically. Impaired wound healing remains a global health concern, leading to chronic wounds, infection, and excessive scarring. This study is the first to evaluate the wound healing potential of topically applied Losartan.

Main methods

Full-thickness excisional wounds were created on Sprague-Dawley rats and treated with topical Losartan (5 % or 10 %), base cream, or left untreated. Wound healing was assessed macroscopically and histologically at days 10, 20, and 30 post-injury. In addition to analyzing myeloperoxidase (MPO), monocyte chemotactic protein-1 (MCP-1), glycosaminoglycans (GAGs), and hydroxyproline, further parameters such as wound closure rate, collagen fiber alignment, revascularization, and inflammatory cell infiltration were evaluated.

Key Findings

Losartan-treated wounds showed significantly accelerated closure, enhanced cytokeratin 14 (CK14) and improved epithelial regeneration, and reduced inflammatory infiltration. MPO activity was notably decreased, especially in early healing, and MCP-1 modulation followed the macrophage dynamics. Histological results demonstrated enhanced fibroblast maturation, revascularization, and organized collagen deposition. Elevated levels of hydroxyproline and GAGs confirmed improved extracellular matrix formation.

Significance

This study is the first to demonstrate the efficacy of topically applied Losartan in promoting wound healing by modulating inflammation, enhancing matrix remodeling, and regulating CK14 expression. These findings support the therapeutic repositioning of Losartan as a novel topical agent and pave the way for its clinical development in the management of chronic wounds, including diabetic and ischemic ulcers.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.