脂肪移植改善光老化的机制研究

Photoaging is a term used for the characteristic changes to skin induced by chronic ultraviolet exposure. Many studies of the prevention of photoaging ison the molecular level, mainly by blocking nuclear factor-kappa B (NF-κB) and /orp38 mitogen-activated protein kinase signaling (p38MAPK) pathway, reducing thedegradation of collagen in the dermis. Autologous fat transplantation has beenextensively studied as a popular facial rejuvenation surgery, and clinical studieshave reported that fat grafts not only improve facial contours as a filler, but also improve the skin texture in the recipient site. Recent researches and our previous work found that the dermis thickness and dermal collagen contents in fat injection sites were increased compared to the control sites. Given adipose-derived mesenchymal stem cells (ASCs)’s skin regeneration effects, they are considered to be the major action cellular components involved. Researches on the anti-photoaging effects of fat grafting are mainly clinical cases reports, experimental studies are rare, and the specific molecular mechanism is unclear. Our study will apply fat grafting on photoaging animal model to explore the effects of grafted fat on the skin histologic changes and the skin molecular regulations of p38MAPK and NF-κB signal transduction pathway. Besides, further researches on ASCs’ effects to p38MAPK and NF-κB pathway moleculars will be made by establishing in vitro photoaging model. The studies will have important theoretical significance in broadening fat grafting clinical application

光老化是指由紫外线长期照射引起的皮肤老化。很多防治光老化的研究主要通过NF-κB和/或p38MAPK通路，减少真皮内胶原的降解。自体脂肪移植广泛应用于面部年轻化治疗，临床研究报道移植的脂肪不仅可改善面部轮廓，还可改善皮肤质地。最近研究和我们的前期工作发现脂肪注射部位的皮肤真皮增厚、胶原含量增加。由于脂肪间充质干细胞（ASCs）具有皮肤再生作用，被认为是参与该作用的主要细胞成分。目前脂肪移植改善皮肤光老化的研究多为临床病例观察，实验研究尚少，且具体分子机制不明。本课题将脂肪移植应用于皮肤光老化动物模型，观察脂肪移植对光老化皮肤的组织学影响，探讨脂肪移植对真皮p38MAPK 和 NF-κB 信号传导通路的影响。建立体外光老化模型进一步验证ASCs对真皮成纤维细胞p38MAPK 和 NF-κB 信号传导通路影响。本研究为光老化治疗和脂肪移植在面部年轻化领域的应用提供理论依据。

自体脂肪组织不仅可作为填充物改善术区轮廓，还具有改善皮肤质地的作用。该作用是否与脂肪组织中的脂肪间充质干细胞（ADSCs）有关一直是大家关注的焦点，相关机制有待进一步研究。本研究选取在光老化皮肤治疗方面临床实用性更高的纳米脂肪进行研究，研究发现相比传统纳米脂肪，注射离心富集SVF/ADSC的纳米脂肪可有效改善皮肤光老化，同时证明了SVF/ADSC在脂肪移植改善光老化中作用。进一步地，ADSC分泌的外泌体（ADSC-exosomes）可能是移植的脂肪发挥其改善皮肤光老化作用的重要途径。本课题的发现，可为脂肪移植用于光老化治疗提供理论依据，为纳米脂肪的面部年轻化治疗方案提供新思路，从而推动纳米脂肪在面部年轻化中的临床应用。