真皮白色脂肪組織在放射性皮膚炎發展中的角色

Abstract

放射性治療是為了有效去除癌細胞的治療方法之一，然而在治療的同時卻也會造成正常細胞的損傷，在皮膚可引起放射性皮膚炎，對癌症患者造成二次傷害。儘管放射性治療已於臨床上運用一百多年，但截至目前對於放射性皮膚炎的確切機制仍不清楚。過去的研究發現，在放射線傷害後，小鼠脂肪組織內脂肪細胞會縮小。此研究中，我們探討此現象是否與放射性皮膚炎的發病有關。我們看到嚴重的放射性皮膚炎出現之前，皮膚的真皮白色脂肪組織會先有發炎現象，並且同時伴隨有脂肪細胞變小。我們透過免疫螢光染色的方法，發現巨噬細胞、Ｔ細胞以及嗜中性球在放射性皮膚炎的發病過程在皮膚中會逐漸增加，最後出現皮膚發炎及潰爛的現象。我們猜想放射線誘發真皮白色脂肪組織脂肪分解，而真皮白色脂肪組織脂肪分解可能會惡化放射線皮膚炎。我們透過藥物及基因轉殖小鼠抑制真皮白色脂肪組織脂肪分解，觀察到可以放射線傷害後小鼠皮下的脂肪細胞並未有縮小的現象產生，同時也減輕了放射線皮膚炎的症狀。我們也探討免疫細胞在誘發真皮白色脂肪組織脂肪分解以及放射線皮膚炎的角色。我們的結果顯示脂肪組織與免疫細胞的交互作用，可能是惡化放射線皮膚炎的可能原因。未來可以更深入探討這樣的交互作用，如何惡化放射線皮膚炎的詳細分子機制。

Radiotherapy not only kill cancer cells, but also damage normal cells. In skin, it often leads to radiation dermatitis that causes secondary damage to cancer patients. Although radiation therapy has been used clinically for more than 100 years, the exact mechanism of radiation dermatitis remains unclear. Prior research showed that adipocytes in mouse adipose tissue shrink after radiation damage. In this study, we investigated whether this phenomenon is related to the development of radiation dermatitis. We found that, before severe radiation dermatitis occurred, the skin dermal white adipose tissue first became inflamed, and at the same time, the adipocytes also became shrank in size. Through immunofluorescence staining, we found that macrophages, T cells, and neutrophils gradually increased in the skin during the development of radiation dermatitis, and eventually skin ulceration occurred. We speculated that radiation induces dermal white adipose tissue lipolysis and that dermal white adipose tissue lipolysis may worsen radiation dermatitis. We used drugs and genetically modified mice to inhibit lipolysis in dermal white adipose tissue and observed that adipocytes in dermal white adipose tissue did not shrink after radiation damage, and the signs of radiation dermatitis were also alleviated. We also explored the role of immune cells in inducing dermal white adipose tissue lipolysis and radiation dermatitis. Our results suggest that the interaction of dermal white adipose tissue with immune cells may play a possible role in worsening radiation dermatitis. The detailed molecular mechanisms of how such interactions worsen radiation dermatitis can be explored in more depth in the future.