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光动力疗法对皮肤瘢痕和膨胀纹影响的体外评估

Ex vivo evaluation of the effect of photodynamic therapy on skin scars and striae distensae.

作者信息

Mendoza-Garcia Jenifer, Sebastian Anil, Alonso-Rasgado Teresa, Bayat Ardeshir

机构信息

Bioengineering Group, School of Materials, The University of Manchester, Manchester, UK.

Plastic & Reconstructive Surgery Research Group, Manchester Institute of Biotechnology (MIB), The University of Manchester, Manchester, UK.

出版信息

Photodermatol Photoimmunol Photomed. 2015 Sep;31(5):239-51. doi: 10.1111/phpp.12180. Epub 2015 Jun 1.

Abstract

BACKGROUND

Skin scars and striae distensae (SD) are common dermal disorders with ill-defined treatment options. There is emerging clinical evidence for use of photodynamic therapy (PDT) in treating skin fibrosis. Therefore, the aim here was to investigate the effect of PDT on skin scars and SD in an ex vivo model of human skin scarring.

METHODS

Photodynamic therapy, with 5ALA or MALA in addition to illumination with 40 J/cm(2) of red light, was applied to striae alba, fine line, hypertrophic and keloid scars ex vivo (n = 18). General morphology was assessed by H&E, Herovici's and Weigert's differential staining. Apoptosis, proliferation, metalloproteinase 3 and tropoelastin expression were quantified immunohistochemically, and differential gene expression of proliferating cell nuclear antigen (PCNA), collagen (COL) type I and type III, matrix metalloproteinase 3 (MMP3) and tropoelastin (ELN) was assessed by real-time quantitative reverse transcription polymerase chain reaction.

RESULTS

Apoptosis increased, which correlated with decreased proliferation and PCNA gene expression. Post-PDT, matrix components were found to be re-organised in both hypertrophic and keloid scars. COLI and COLIII gene expression levels decreased, whilst MMP3 and ELN increased significantly post-PDT compared to normal skin and untreated controls (P < 0.05). However, no significant difference between 5ALA and MALA-PDT treatments was observed.

CONCLUSION

Using our unique ex vivo model, we show for the first time morphological and cellular effect of application of PDT, which correlates with the degree and severity of dermal fibrosis. In view of this, PDT may be ideal in targeting treatment of abnormal skin scarring.

摘要

背景

皮肤瘢痕和膨胀纹是常见的皮肤疾病,治疗方法尚不明确。有新的临床证据表明光动力疗法(PDT)可用于治疗皮肤纤维化。因此,本研究旨在探讨光动力疗法对人皮肤瘢痕形成的体外模型中皮肤瘢痕和膨胀纹的影响。

方法

将5-氨基乙酰丙酸(5ALA)或甲酯化5-氨基乙酰丙酸(MALA)联合40 J/cm²红光照射应用于体外白色膨胀纹、细线状瘢痕、增生性瘢痕和瘢痕疙瘩(n = 18)。通过苏木精-伊红(H&E)染色、赫罗维奇(Herovici)染色和魏格特(Weigert)染色评估一般形态。免疫组织化学法定量检测细胞凋亡、增殖、基质金属蛋白酶3和原弹性蛋白的表达,并通过实时定量逆转录聚合酶链反应评估增殖细胞核抗原(PCNA)、I型和III型胶原(COL)、基质金属蛋白酶3(MMP3)和原弹性蛋白(ELN)的差异基因表达。

结果

细胞凋亡增加,这与增殖和PCNA基因表达降低相关。光动力治疗后,增生性瘢痕和瘢痕疙瘩中的基质成分均发生重新组织。与正常皮肤和未治疗的对照组相比,光动力治疗后I型和III型胶原基因表达水平降低,而MMP3和ELN显著增加(P < 0.05)。然而,未观察到5ALA和MALA光动力治疗之间的显著差异。

结论

使用我们独特的体外模型,我们首次展示了光动力疗法应用的形态学和细胞效应,这与皮肤纤维化的程度和严重程度相关。鉴于此,光动力疗法可能是针对异常皮肤瘢痕治疗的理想方法。

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