2ME2通过氧感知通路（HIF-1α/VHL）抑制瘢痕疙瘩生长及机制研究

氧感知通路是组织细胞对环境氧进行反应的重要通路，HIF-1α是该通路中的关键靶点，其下游效应通路更决定了组织细胞的生理状态。有研究表明，瘢痕疙瘩组织处于乏氧微环境，我们通过2ME2对瘢痕疙瘩成纤维细胞效应的前期研究中发现，2ME2可以改善乏氧瘢痕疙瘩成纤维细胞HIF-1α、VEGF等氧感知通路及其下游效应通路关键因子的表达，因此我们提出了2ME2能够通过影响氧感知通路抑制瘢痕疙瘩生长的推论。本项目将首先系统而全面地分析瘢痕疙瘩组织氧感知通路的激活状态和激活水平，然后通过建立体外乏氧细胞模型探讨2ME2对氧感知通路及其下游效应通路的影响和作用机制，最后通过裸鼠移植瘢痕疙瘩模型研究2ME2对活体生命体征的影响并验证其体内效应。本项目所获得的信息将有助于阐明2ME2治疗瘢痕疙瘩的分子机制，为2ME2的临床应用提供新的思路和理论依据，从而推进整形外科新型专科用药的研发。

Oxygen-sensing signal pathway is a paramount pathway for tissue cells responding to environmental oxygen, in which HIF-1α is the key target. Its downstream pathways also determine tissue cells’ physiological state. Former studies proved hypoxia microenvironment exists in keloid tissue. Our previous studies demonstrated that 2ME2 could decrease HIF-1α and VEGF expression of oxygen-sensing signal pathway and its downstream pathways in hypoxia keloid fibroblasts. In this case, we infer that 2ME2 could inhibit keloid development through oxygen-sensing signal pathway. In this project, we firstly analyze oxygen-sensing pathway activation status and levels in human keloid tissue systematically and comprehensively. Then, culture hypoxia keloid fibroblasts in vitro to explore the effect and mechanism of 2ME2 towards oxygen-sensing signal pathway and its downstream pathways. Finally, establish keloid model in nude mice to assess and verify 2ME2’s effect in vivo. This project will be conducive to clarify molecular mechanism of 2ME2 in treating keloid, provide scientific theoretical basis for 2ME2 clinical application, promote development of new specialized drug for plastic surgery.