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ALA-PDT 对体内外伤口愈合中巨噬细胞的影响及其相关机制。

Effects of ALA-PDT on the macrophages in wound healing and its related mechanisms in vivo and in vitro.

机构信息

Department of Dermatology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.

State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China; Chongqing Key Laboratory for Disease Proteomics, Chongqing 400038, China.

出版信息

Photodiagnosis Photodyn Ther. 2022 Jun;38:102816. doi: 10.1016/j.pdpdt.2022.102816. Epub 2022 Apr 1.

Abstract

BACKGROUND

Several studies have suggested the effectiveness of photodynamic therapy (PDT) for wound healing. Macrophages are critical immune cells necessary for regulated inflammation during wound repair. However, the available information regarding the effects of PDT on macrophages during cutaneous wound healing remains insufficient. This study aimed to further investigate these aspects in vivo and in vitro.

METHODS

Mouse full-thickness wound models were used as the study samples to investigate the therapeutic effects and mechanisms of 5-aminolevulinic acid (ALA) PDT. Wound healing rate, granulation tissue formation, local inflammation, M1/M2 macrophages differentiation, were measured at different time points treated by ALA-PDT. The polarization of macrophages induced by ALA-PDT was further evaluated in vitro using PCR and western blot analysis.

RESULTS

ALA-PDT could promote formation of granulation tissue, increase inflammatory infiltration and activate M1 macrophages in the early stage of injury. While, ALA-PDT could also facilitate absorption of granulation tissue, inhibit inflammatory infiltration and enhance M2 macrophages polarization in the later stage of wound repair. In vitro, ALA-PDT could modulate the ratio of M2 polarization to M1 polarization via NF-κB signaling pathway.

CONCLUSIONS

ALA-PDT topical application stimulates wound healing by regulating formation of granulation tissue, inflammatory process and M1/M2 macrophages differentiation. The study places a preliminary theoretical basis for topical ALA-PDT to be administered clinically in cutaneous wounds healing.

摘要

背景

多项研究表明光动力疗法(PDT)对伤口愈合有效。巨噬细胞是伤口修复过程中调节炎症所必需的关键免疫细胞。然而,关于 PDT 对皮肤伤口愈合过程中巨噬细胞的影响的信息仍然不足。本研究旨在体内和体外进一步研究这些方面。

方法

使用小鼠全层伤口模型作为研究样本,以研究 5-氨基酮戊酸(ALA)PDT 的治疗效果和机制。在不同时间点通过 ALA-PDT 处理后,测量伤口愈合率、肉芽组织形成、局部炎症、M1/M2 巨噬细胞分化。使用 PCR 和 Western blot 分析进一步评估 ALA-PDT 诱导的巨噬细胞极化。

结果

ALA-PDT 可促进肉芽组织形成,增加损伤早期的炎症浸润并激活 M1 巨噬细胞。然而,ALA-PDT 也可以促进肉芽组织吸收,抑制炎症浸润,并增强伤口修复后期的 M2 巨噬细胞极化。在体外,ALA-PDT 可以通过 NF-κB 信号通路调节 M2 极化与 M1 极化的比值。

结论

ALA-PDT 局部应用通过调节肉芽组织形成、炎症过程和 M1/M2 巨噬细胞分化来刺激伤口愈合。该研究为临床应用局部 ALA-PDT 治疗皮肤伤口愈合提供了初步的理论基础。

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