基于Sirt1/FoxO1介导的自噬途径探讨七叶胆苷XVII保护糖尿病视网膜病Müller细胞损伤的分子机制

视网膜Müller细胞损伤是糖尿病视网膜病（diabetic retinopathy, DR）形成的关键环节。前期研究发现七叶胆苷XVII（Gypenoside XVII, GP-17）具有较强的抗氧化、抗凋亡、自噬调控，保护血管内皮细胞损伤活性。Sirt1/FoxO1信号通路在氧化应激损伤介导的细胞自噬中扮演了重要的调节作用。由此提出假说：GP-17能够通过调控Sirt1/FoxO1介导的细胞自噬保护DR中Müller细胞氧化损伤。为验证该假说，从整体和细胞分子水平探讨GP-17对DR的保护作用，并从自噬与凋亡角度探讨GP-17对Sirt1/FoxO1的信号通路的调控作用。旨在阐明GP-17抑制DR的分子机制，也为DR防治研究提供新的靶点。

Retinal Müller cell injury is the key step in the development of Diabetic retinopathy (DR). It has been reported that Gypenoside XVII (GP-17) exerts strong anti-oxidative, anti-apoptotic activities, modulates cell autophagy and protects vascular endothelial cell injury. Sirt1/FoxO1 signal pathway plays an important role in oxidative stress induced autophagy modulation. Accordingly, we propose that GP-17 prevents Müller cell oxidative injury by regulating Sirt1/FoxO1-mediated autophagy in DR. To demonstrate this hypothesis, we investigate the protective effects of GP-17 via establishing different molecular, cellular, and animal levels. Moreover, with cell autophagy and apoptosis, we explore the modulatory effects of GP-17 on Sirt1/FoxO1 pathway in injured Müller cell. It’s our purpose to elucidate the molecular mechanism of GP-17 on DR inhibition. Meanwhile, it provides a new target for DR treatment.