增生性瘢痕（HS）作为临床治疗的难题，是研究的重点和难点。目前对IL-10功能的研究主要集中在抗炎反应与免疫抑制两个方面，但最新文献及我们的研究表明：IL-10能改善瘢痕外观，拮抗瘢痕的形成，赋予了IL-10抗瘢痕纤维化的新功能。我们深入的研究表明：HS及HSFs的pAKT和pSTAT3较NS及NSFs存在明显差异；IL-10呈量─效关系调控HSFs中pAKT及pSTAT3；且AKT与STAT3交互调控。因此，有必要深入阐明IL-10拮抗瘢痕纤维化的作用机制。鉴于此，本研究拟用IL-10过表达及沉默的HSFs，证实IL-10拮抗瘢痕纤维化之功能；分析HSFs的pAKT及pSTAT3，探讨IL-10对AKT/mTOR与STAT3通路关键分子的调控作用；并用通路抑制剂/siRNA对细胞及动物验证。该课题的实施有望阐明IL-10拮抗瘢痕纤维化的作用机制，为HS的预防、治疗及药物筛选奠定基础。

Hypertrophic scar (HS), as a serious skin fibrotic disease, has always been a major problem for clinical treatment. The current research about the biological functions of interleukin 10 (IL-10) mainly focus on immunosuppressive and anti-inflammatory, and have elucidated the important regulation mechanisms in inflammatory and immune response. Reports and our research showed that IL-10 plays a pivotal role in wound healing, and has been identified as a prospective scar-improving therapeutic cytokine. These data demonstrate that IL-10 has a novel biological role in anti-fibrosis in wound healing. However, relatively little is known about the molecular mechanism on IL-10-mediated anti-fibrosis and scar-improvement effects. In accordance with extensive publication, our result revealed that the phosphorylation levels of AKT and STAT3 in HS tissue and HS fibroblasts (HSFs) have significant differences with that in corresponding normal skin (NS) tissue and NS fibroblasts (NSFs). And we founded that IL-10 could dose-dependently regulate the phosphorylation levels of AKT and STAT3 in HSFs. It is widely believed that PI3K/AKT/mTOR pathway is involved in the regulation of cell proliferation, differentiation, apoptosis and other physiological activities, and IL-10 plays biological function through STAT3 pathway via specific receptor (IL-10R) on cell surface. For these reasons, HSFs with IL-10 over-expression (HSFs-IL10+) and IL-10 silence (HSFs-IL10-) will be used in this study to confirm the anti-fibrosis role of IL-10; to explore the regulatory effect of IL-10 on PI3K/AKT/mTOR and STAT3 pathways; and further to validate the anti-fibrosis role of IL-10 in both cellular and rabbit ear HS model by molecular inhibitors/siRNAs. This study will elucidate the novel molecular mechanism of IL-10 in protection against scar fibrosis, and further lay foundation for the prevention, treatment and drug screening of HS.