纳米自组装糖肽通过靶向诱导M2巨噬细胞凋亡抑制肾脏纤维化进展的研究

肾脏纤维化是急性肾损伤病理性修复的结局，表现为正常组织被大量肌成纤维细胞及细胞外基质所代替，肾功能持续降低并最终丧失。M2型巨噬细胞是肾脏纤维化的重要促进者，通过产生促生长因子及转分化为肌成纤维细胞，促进纤维化微环境形成。但如何时空特异性调控M2巨噬细胞的功能及数量是目前研究的难点。纳米自组装技术通过双重靶向及体内自组装效应，进行组织高特异靶向富集和功能调控。本研究利用该技术合成纳米自组装糖肽，特异性诱导肾间质M2巨噬细胞凋亡，实现对纤维化微环境的精确调控，阻断肾脏纤维化进展。通过改变纳米自组装糖肽的干预时间，寻找M2巨噬细胞从促进组织修复向促进纤维化的关键转变点，揭示肾脏纤维化微环境中M2巨噬细胞及其他免疫细胞功能的动态变化，为慢性炎症导致肾脏纤维化提供新的治疗方案。

Renal fibrosis is the outcome of pathological repair of acute kidney injury (AKI), in which the normal tissue structure is replaced by numerous myofibroblasts and extracellular matrix, and induces constantly loss of renal function. Alternatively activated macrophages (M2) is an important activator in the progress of renal fibrosis by producing various growth factors and trans-differentiating into myofibroblasts. However, how to specifically regulate the function and quantity of M2 macrophages from the dimension of both time and space is still a problem. Self-assembled nano-material is a novel technology, which enrich in specific tissue microenvironment and modulate cell function through the mechanism of double-targeting and in vivo self-assembly. In this study, we prepare a self-assembled nano-glycopeptide, which targets renal interstitial M2 macrophages in the microenvironment and ameliorate renal fibrosis by inducing apoptosis of the pro-fibrotic macrophages. By administrating the nano-glycopeptide in a time-dependent fashion, we try to identify the specific time point when M2 macrophages adopt a pro-fibrotic phenotype rather than a pro-healing phenotype. Moreover, we try to decipher the dynamic roles the other immune cells play in this whole process. This project will hopefully produce a new solution for the treatment of chronic inflammation related renal fibrosis.