CXCL8放大炎症反应介导ALA-PDT治疗重度痤疮的机制研究

Severe acne is a chronic inflammatory dermatosis of pilosebaceous units which has refractory and scar tendency. ALA-PDT is a safe and effective treatment for severe acne, however, the specific mechanism of the ALA-PDT in acne is not yet clear. Clinically, intense inflammatory reaction such as erythema and pustule occurs in the early phase after ALA-PDT, and there is a positive correlation between the degree of inflammatory reaction and the efficacy. In our previous study, we found that chemokine CXCL8 in acne lesions was significantly upregulated after ALA-PDT in 24h, which can recruit neutrophils and induce acute inflammatory response. Therefore, we speculated that increased CXCL8 with amplifying inflammation response may be the key to the efficacy of ALA-PDT. This study was designed to investigate the role of CXCL8 amplifying inflammation response induced by ALA-PDT in the treatment of severe acne in vivo and in vitro, and to further explore the possible mechanism of the upregulation of CXCL8 induced by ALA-PDT using the rabbit ear acne model and cell culture. Our study may provide a reliable theoretical basis for the clinical application and optimization of ALA-PDT in the treatment of severe acne.

重度痤疮是一种毛囊皮脂腺的慢性炎症性皮肤病，迁延难愈，易留瘢痕，治疗棘手。ALA-PDT治疗重度痤疮起效快、安全有效。临床上，ALA-PDT后痤疮治疗区域出现红斑、脓疱等强烈的急性炎症，且炎症反应程度与疗效呈正相关，但具体机制不明。我们的前期研究发现，ALA-PDT后痤疮皮损内趋化因子CXCL8表达显著上调，后者是中性粒细胞最重要的趋化因子，可诱导急性炎症。因此，我们提出科学假说：CXCL8放大炎症反应，打破慢性炎症胶着状态可能是ALA-PDT治疗重度痤疮的关键所在。为证实以上设想，本研究拟应用临床标本分析、兔耳痤疮模型、体外细胞培养以及分子生物学技术，从组织、细胞与分子水平验证ALA-PDT诱导CXCL8放大炎症反应的过程，并进一步探索CXCL8上调的可能分子机制，为今后临床应用并优化ALA-PDT治疗重度痤疮提供可靠的理论依据。

重度痤疮是一种毛囊皮脂腺的慢性炎症性皮肤病，迁延难愈，易留瘢痕。ALA-PDT治疗重度痤疮起效快、安全有效，但其具体治疗机制尚不明确。临床上，ALA-PDT后痤疮治疗区域出现红斑、脓疱等强烈的急性炎症，然后重度痤疮皮损逐渐得到改善。本课题组系统评估了ALA-PDT治疗痤疮的疗效与不良反应的关系，发现皮损清除率与红斑等炎症反应程度存在一致性关系，提示ALA-PDT放大炎症与改善重度痤疮相关。.我们的前期研究发现，ALA-PDT后痤疮皮损趋化因子CXCL8表达显著上调，后者是中性粒细胞最重要的趋化因子，可诱导急性炎症；因此，我们提出科学假说：CXCL8放大炎症反应，打破慢性炎症胶着状态可能是ALA-PDT治疗重度痤疮的关键所在。.为证实以上猜想，我们应用临床标本、动物模型、体外细胞培养以及分子生物学技术，从组织水平、动物水平和细胞水平上验证了ALA-PDT均能上调CXCL8的表达，且从动物水平上观察到不同时间点（0，1，3，6，12，24h）ALA-PDT募集炎症细胞放大炎症的过程，并进一步探索CXCL8上调的可能分子机制。研究结果发现ALA-PDT通过p38 MAPK通路上调了CXCL8的表达，这种上调作用可被p38抑制剂阻断。本研究初步解释了ALA-PDT治疗重度痤疮后急性炎症反应的机制及应用ALA-PDT放大炎症反应改变痤疮慢性病程从而治疗痤疮的可行性。