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5-氨基酮戊酸光动力疗法通过诱导皮脂腺细胞线粒体应激和氧化损伤来抑制脂质分泌,改善小鼠耳痤疮。

5-Aminolaevulinic acid-based photodynamic therapy suppresses lipid secretion by inducing mitochondrial stress and oxidative damage in sebocytes and ameliorates ear acne in mice.

机构信息

Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.

Department of Dermatology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.

出版信息

Int Immunopharmacol. 2024 Oct 25;140:112795. doi: 10.1016/j.intimp.2024.112795. Epub 2024 Aug 3.

Abstract

Acne is a chronic inflammatory skin disease with wide-ranging effects, involving factors such as Propionibacterium acnes (P. acnes) infection and sebum hypersecretion. Current acne treatments are challenged by drug resistance. 5-aminolaevulinic acid (ALA) -based photodynamic therapy (PDT) has been widely used in the clinical treatment of acne, however, the mechanism of its action remains to be elucidated. In this study, by constructing a mice ears model of P. acnes infection, we found that ALA-PDT inhibited the proliferation of P. acnes in vivo and in vitro, significantly ameliorated ear swelling, and blocked the chronic inflammatory process. In vitro, ALA-PDT inhibited lipid secretion and regulated the expression of lipid synthesis and metabolism-related genes in SZ95 cells. Further, we found that ALA-PDT led to DNA damage and apoptosis in SZ95 cells by inducing mitochondrial stress and oxidative stress. Altogether, our study demonstrated the great advantages of ALA-PDT for the treatment of acne and revealed that the mechanism may be related to the blockade of chronic inflammation and the suppression of lipid secretion by ALA-PDT.

摘要

痤疮是一种慢性炎症性皮肤病,具有广泛的影响,涉及痤疮丙酸杆菌(P. acnes)感染和皮脂过度分泌等因素。目前的痤疮治疗方法面临着耐药性的挑战。5-氨基酮戊酸(ALA)为基础的光动力疗法(PDT)已广泛应用于痤疮的临床治疗,但作用机制仍有待阐明。在这项研究中,我们通过构建痤疮丙酸杆菌感染的小鼠耳部模型发现,ALA-PDT 抑制了体内和体外痤疮丙酸杆菌的增殖,显著改善了耳部肿胀,并阻断了慢性炎症过程。在体外,ALA-PDT 通过诱导线粒体应激和氧化应激,抑制 SZ95 细胞中的脂质分泌并调节脂质合成和代谢相关基因的表达。此外,我们发现 ALA-PDT 通过诱导 DNA 损伤和细胞凋亡,抑制 SZ95 细胞的脂质分泌。总的来说,我们的研究证明了 ALA-PDT 在治疗痤疮方面的巨大优势,并揭示了其机制可能与阻断慢性炎症和抑制脂质分泌有关。

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