Irisin经自噬对高糖环境下血管内皮功能的保护作用及机制

血管内皮细胞功能损伤是糖尿病弥漫性血管病变的基础与始动环节，是防治的核心。新发现的因子Irisin具有代谢调控作用，为糖尿病及血管并发症的防治提供了新的思路。我们前期临床观察发现2型糖尿病患者irisin水平降低且与血管内皮细胞相关联。然而irisin是否能直接作用于血管内皮，调节其功能，国内外尚未见报道。我们进行了体外实验，利用重组Irisin直接刺激高糖环境下血管内皮细胞，发现其激活自噬，减轻氧化应激，保护血管内皮细胞功能，但具体机制尚不明确。本研究思路来源于临床发现，以前期研究为基础，提出"Irisin通过AMP激活自噬保护高糖环境下内皮细胞功能"的研究假设，采用内皮细胞及内皮特异性自噬基因敲除小鼠为模型，从分子、细胞、组织及动物多层次观察irisin对高糖环境下血管内皮功能的影响，并从自噬及相关信号通路探讨其调控机制，以期为临床糖尿病血管病变的早期干预策略提供新的思路和理论支持。

Hyperglycemia induced vascular endothelial cells dysfunction contributes to the development of cardiovascular complications of diabetes, which is the key point of prevention. Irisin, a newly identified hormone reported in Nature 2012, has been reported to have notable effect on lipid metabolism and be a new potential target for the treatment of type 2 diabetes and its complications. Our prelimitary study showed that serum irisin levels were decreased in type 2 diabetes patients and associated with endothelial cell functions,suggesting irisin may play a crucial role in the regulation of endothelial cell functions. Furthermore, we found that irisin improved hyperglycemia induced endothelial cell dysfunction in vitro via autophagy activation. However, the effect of irisin in vivo has yet to be explored and the molecular mechanism is not clear. In this study, we will use endothelial cell and autophagy gene knockout mice as study models, to explore the effect of irisin on hyperglycemia induced vascular endothelial dysfunction and explore the mechanisms involved. The outcome will not only shed light on a hormetic nature of irisin in diabetes, but also provide novel perspectives to therapy of diabetes vascular complications.