血管性病变是糖尿病，高血压及高血脂等代谢性疾病的主要并发症。而上述代谢性疾病可引起血管内皮组织破坏，使得内皮依赖的血管功能调控药物在治疗血管性病变过程中效果不佳，因此急需研究与开发对血管内皮具有修复作用，且非内皮依赖的血管功能调控药物。本申请拟设计和开发一系列基于一氧化氮与硫化氢信号通路应答机制的药物，即在前期开发的钩藤碱衍生物G2/G3（具有上调一氧化氮合成酶eNOS的表达，修复血管内皮功能的作用）结构基础上进一步引入调控硫化氢释放的分子片段——在内皮损伤的病理条件下，硫化氢不仅可诱导一氧化氮从稳定的非内皮依赖的“一氧化氮库”中释放，还可以调控一氧化氮下游通路，成为为血管活性物质NO的重要补充。期望通过内皮修复加非内皮依赖调控的双重作用达到有效治疗和预防代谢性疾病引发的血管性病变的目的，并为一氧化氮与硫化氢信号通路应答机制的进一步深入研究提供强有力的研究工具。

Vascular lesion is the main complication of metabolic diseases such as diabetes, hypertension and hyperlipidemia. Clinical studies have shown that the destruction of endothelial tissue caused by metabolic diseases leads to the inefficiency of endothelium-dependent vascular function modulating drugs. Therefore, it is urgent to develop the non-endothelium-dependent vascular function regulating drugs. This application plans to develop a series of drugs based on the crosstalking between nitric oxide and hydrogen sulfide pathway, through the upregulation of the expression of eNOS to repair vascular endothelial cells by the derivatives of rhynchophylline, and at the same time, by use of hydrogen sulfide regulation or release fragment to induce nitric oxide further releasing via non-endothelial-dependent pathway. Hopefully, these researches would provide dual effects drug candidates (repairing vascular endothelial cells and regulating vascular functions via non-endothelial-dependent pathway) for the treatment of vascular lesion and powerful tools for further study of nitric oxide and hydrogen sulfide pathway response mechanism.