内皮细胞功能紊乱导致的血管并发症是糖尿病患者死亡的主要原因，目前临床缺乏既能控制血糖又能直接干预糖尿病血管病变的多靶点药物。最新研究发现NO激活组蛋白去乙酰化酶SIRT1能够调控内皮细胞功能紊乱。通过前期大量合成和筛选，我们发现了同时具备降糖和NO释放活性的NO供体型α糖苷酶抑制剂TsPA-NO。本研究拟采用NO特异性感测技术研究TsPA-NO对自发性2型糖尿病大鼠体内活性NO水平的动态调节作用，为通过补充NO防治糖尿病血管并发症提供依据；通过TsPA-NO对氧化应激水平、炎症反应的调节研究，阐明其血管内皮保护的功能；并进一步在细胞分子水平开展相关机制研究，明确TsPA-NO通过抗炎及改善氧化应激而产生的血管保护效应由SIRT1信号通路介导。本课题不仅阐释TsPA-NO对血管内皮的保护作用及保护机制，而且能够为糖尿病多靶点治疗药物的开发提供实验基础和理论依据。

For the death of diabetic patients, vascular complications induced by endothelial dysfunction are the leading causes. Multi-target drugs are the urge need for the clinic to control hyperglycemia with the vascular complications be directly intervened. The activation of histone deacetylase SIRT1 by NO, is a new regulation approach of the endothelial dysfunction. Before this application, based on plenty synthesis and screening works, we found TsPA-NO, a α-glucosidase inhibitor with nitric oxide donor , which exhibited hypoglycemic and NO-releasing activity. In this study, NO specific sensing technique will be utilized to clarify the regulatory effect of TsPA-NO in type II diabetic rats, providing some basis for NO supplement therapy to treat diabetic cardiovascular complications. By the investigation of oxidative stress and inflammatory response, we will confirm the protective effect of the blood vessel endothelium by TsPA-NO. Moreover, in the followed study we would clarify the endothelial protective effect of TsPA-NO may be mediated via SIRT1 related signaling pathway. From this study, not only the NO mediated protective functions and mechanisms of TsPA-NO to the vascular endothelium will be presented, but also the experimental and theoretical basis for the design and development of multi-target antidiabetic dugs will be provided.