人参皂苷Rg3长效缓释纤维膜抑制疤痕增生的信号传导通路研究

Hypertrophic scar (HS) is one of the most common diseases of plastic surgery, and its treatment is often through inhibition of fibroblasts proliferation and suppression of excessive neovascularization. Currently, the main treatment of HS is drug injection, among which the most popular drugs are steroids and anti-tumor drugs. However, these two drugs are not ideal, because they are associated with several unwanted disadvantages including side effects and requirement for repetitive injections over several months. Ginsenoside Rg3 (Rg3) is a kind of antitumor Chinese medicine, which can induce many kinds of tumor cells apoptosis. What is more, Rg3 is a safe drug, which won't result in toxic side effects. Our preliminary experiments has prepared a biodegradable GS-Rg3-loaded poly(l-lactide) (PLA) nano-fibrous membranes and found that it can inhibit fibroblasts proliferation, reduce neovascularization, and thus inhibit the early formation of HS and later hyperplasia of HS. However, the continuous releasing time of Rg3 in such nano-fibrous membranes is too short, and the specific HS-inhibiting mechanism of Rg3 remains unclear. Therefore, in this study, we are about to prepare an ellectrospun fibers carrying both Rg3 and mesoporous silica nanoparticles, which can continuously release Rg3 for more than 3 months. The inhibiting effect of HS would be evaluated, and the specific mechanisms would be studied. The interfering of Wnt/b-cateni signaling path would be discussed, the inhibition of HIF-1α, COX-2, the NF-κB expression and ERK2 phosphorylation would be specified. Through this study, we hope to develop a promising new traditional Chinese medicine (TCM) for therapy of HS, and to provide a theoretical basis for scientific application of Chinese medicine.

增生性瘢痕（HS）是整形外科常见病，其治疗通过药物抑制成纤维细胞增殖，降低新生血管生成，进而抑制HS增生。目前，主要通过类固醇药物和抗肿瘤药物进行注射治疗，然而，这类药物和剂型存在毒副作用和需反复注射等缺点。人参皂苷Rg3（Rg3）是一种抗肿瘤中药，可诱导多种肿瘤细胞凋亡，且安全无毒副作用。前期，我们制备携载Rg3的纳米纤维膜可以抑制成纤维细胞增殖，减少新生血管生成，从而抑制HS增生。然而，仍存在Rg3释放时间短和作用机制不明确等问题。本项目，构建复合装载Rg3/介孔二氧化硅纳米颗粒的静电纺纤维，实现Rg3的3月以上的长效释放，考察其抑制瘢痕增生的治疗效果，探讨其具体作用机理。明确其对HS形成中Wnt/b-cateni信号通路的干扰作用，及对HIF-1α, COX-2, NF-κB表达及ERK2磷酸化的调控作用。本研究开拓一种抑制增生性瘢痕的新型中药，为我国中药科学化应用提供理论依据。

皮肤病理性瘢痕是整形外科最常见疾病之一， 可导致患者全身多个器官功能的障碍，并严重影响患者外观。积极探求新的毒副作用少的药物用于治疗瘢痕，减轻患者痛苦和经济负担，具有重大意义。本课题在前期动物实验的基础上，进一步明确人参皂苷Rg3抑制瘢痕的效果。同时，从基因和分子细胞水平比较分析collagen I，collagen III，fibronectin，α-SMA，VEGF等细胞因子在病理性瘢痕成纤维细胞中的变化情况，并探索TGF-β/Smad、Erk信号通路在其中的作用。本课题发现，人参皂苷Rg3能在体外抑制病理性瘢痕成纤维细胞的增殖、侵袭、血管化和胶原沉积，在这些生物学过程中TGF-β/Smad和ERK信号通路参与其中。我们的实验结果表明，人参皂苷Rg3可作为一种潜在的能抑制病理性瘢痕形成和生长的药物应用于临床实践中。本研究为临床治疗病理性瘢痕提供了新的诊疗思路和方法。已发表或录用论文10篇。