ALA-PDT激活自噬抑制Toll样受体信号治疗重度痤疮机制研究

Acne Vulgaris is a common chronic inflammatory disease of the pilosebaceous unit, while severe type may even cause scar formation, which has a strong negative impact on the patients’ physiology and psychology. Our team started early to use ALA photodynamic therapy (PDT) to treat acne and has found its advantage of great efficacy and high selectivity. We also found that inflammation modulation plays a key role in the treatment. Recently, the interaction of autophagy and inflammation was reported in inflammatory diseases, including inflammatory skin diseases. Photodynamic therapy may induce autophagy to some extent. Therefore, we speculate that in the ALA-PDT treatment of severe acne, autophagy may be induced to suppress inflammatory response via inhibiting toll-like receptor pathway in acne, thereby to make lesions subsided. This study was designed to investigate the changes of autophagy and inflammation in acne lesions before and after ALA-PDT treatment, and to investigate the autophagy induced by ALA-PDT and its negative regulatory effect on inflammatory response via inhibiting TLR pathway in acne using the rabbit ear acne-like model in vivo and the human sebocytes (SZ95) in vitro. This study aims to explore the possible mechanism of ALA-PDT in the treatment of acne from a new perspective, providing new ideas for enhancing its efficacy with reducing adverse reaction.

痤疮是一种常见的毛囊皮脂腺炎症性疾病，重度痤疮以炎性丘疹、结节囊肿为主，可形成瘢痕，病程反复，治疗棘手，严重影响患者的身心健康。本课题组在国内较早开展ALA-PDT治疗痤疮，发现其具有高选择性、疗效良好等优点，尤其对中重度痤疮安全、有效，同时发现炎症调节在治疗过程中的作用至关重要。细胞自噬与炎症反应相互调控，而光动力疗法可在一定程度上诱导自噬。因此我们推测，ALA-PDT治疗重度痤疮的过程中，可能通过诱导自噬负向调控Toll样受体信号控制痤疮的炎症反应，促进皮损消退。本项研究拟通过检测ALA-PDT治疗前后痤疮皮损中的自噬及炎症变化，并应用兔耳痤疮模型和模拟皮脂腺细胞炎症状态，从体内体外两方面探讨ALA-PDT诱导自噬抑制TLR通路控制炎症反应在治疗痤疮过程中的作用及机制。本项研究从新的角度探讨ALA-PDT治疗重度痤疮的可能机制，为增强其疗效、优化治疗提供新的思路。

痤疮是一种常见的毛囊皮脂腺炎症性疾病，重度痤疮炎症重，以炎性丘疹、结节囊肿为主，可形成瘢痕，病程反复，治疗棘手，严重影响患者尤其是青少年的身心健康。本课题组在国内较早开展ALA-PDT治疗痤疮，发现其具有高选择性、疗效良好等优点，尤其对中重度痤疮安全、有效，同时发现炎症调节在治疗过程中的作用至关重要。.本项目成功构建鼠耳痤疮样炎症模型，构建人皮脂腺细胞系XL-i-20，并模拟ALA-PDT治疗状态，体内体外实验进一步验证ALA-PDT 治疗重度痤疮后的放大炎症现象，并发现ALA-PDT治疗后皮脂腺细胞自噬激活可诱导铁死亡等介导脂质平衡并调控炎症。同时发现ALA-PDT通过上调COX2/TREM1轴诱导巨噬细胞M1极化，改善痤疮M2慢性炎症状态，并通过PGE2/TLR4及NF-κB/MAPK信号通路发挥调节机制。基于ALA-PDT治疗机制的深入研究，尤其是炎症调节及皮脂腺稳态为临床优化参数，提高疗效，减少不良反应提供了理论基础，并与临床研究相结合，以达到最适化和精准化治疗，促进ALA-PDT的推广应用。