糖尿病血管内皮损伤PPAR-γ/NF-κB调控机制及艳山姜挥发油干预作用的实验研究

Diabetic cardiovascular complications (DCCs) are leading cause of mortality and morbidity for diabetic patients. The prevention and therapeutics, as well as pathological mechanism, have been highlighted by many researchers in clinical and basic medical fields. Currently, researchers commonly focus on protecting integrity of structure and function of arterial endothelium, and looking for novel drug targets to prevent against endothelial dysfunction, because the endothelial dysfunction is not only the key pathological process but also the initiating factor in the development and deterioration of DCCs. Accumulated evidences confirmed that DCCs always company with chronic inflammatory pathological process, and PPAR-γ/NF-κB (a nuclear receptor signal pathway) was widely highlighted on the inflammatory pathological process, however, the key molecular target remains poorly understood for regulating PPAR-γ/NF-κB system in endothelial dysfunction induced by diabetes. Alpinia zerumbet (Chinese name is Yanshanjiang) is a natural medicine resources in Guizhou province. Fructus Alpiniae zerumbet, the fruit of Alpiniae zerumbet, was widely used as minority herb for treatment of cardiovascular diseases in Guizhou Province. The essential oil from Fructus A. zerumbet (EOFAZ) is bioactive ingredients, which could protect against the endothelial cell injury induced by hyperglycemia via inhibiting the inflammatory cytokines. At present, the animal and cellular diabetic vascular dysfunction model were reproduced, and we will further explore the modulating novel mechanism of PPAR-γ/NF-κB in diabetic vascular injury process and the ameliorated effect of EOFAZ with pharmacological agonist and antagonist, and gene transfection technic methods. The present research will provide the molecular target and novel theory for preventing and therapeutic diabetic vascular injury in clinic. Furthermore, we elucidated the protection effects of EOFAZ and relevant mechanism, which would provide the experimental basis and theoretical guidance for exploring the novel pharmacological effects and promoting modern research of ethno-drug, and for traditional folk medicine in-depth research and development.

糖尿病心血管并发症（diabetic cardiovascular complications, DCCs）是糖尿病致死致残的主要病因。血管内皮损伤是DCCs发展与恶化的关键环节与始动因素，保护内皮结构与功能的完整性，寻找内皮损伤防治关键靶位及治疗药物成为研究的焦点。炎症贯穿于DCCs始终，PPAR-γ/NF-κB调控炎症在内皮损伤的作用引起广泛的重视，其确切机制亟待阐明。前期证实贵州地产特色民族药——艳山姜挥发油（EOFAZ）对高糖诱导内皮细胞损伤具有显著的保护作用，其机制与抑制炎症因子表达相关。本研究以EOFAZ为研究对象，建立细胞与动物实验模型，采用激动剂与拮抗剂及基因转染技术，探索调控PPAR-γ/NF-κB的关键分子，为糖尿病内皮损伤防治提供新的靶位与理论指导，阐明EOFAZ防治糖尿病内皮功能障碍的作用及机制，证实民族药新药理作用及作用机制，为其深层次研究奠定理论指导和实验基础。

糖尿病心血管并发症（diabetic cardiovascular complications, DCCs）是糖尿病致死致残的主要病因。血管内皮损伤是DCCs发展与恶化的关键环节与始动因素，保护内皮结构与功能的完整性，寻找内皮损伤防治关键靶位及治疗药物成为研究的焦点。炎症贯穿于DCCs始终，PPAR-γ/NF-κB调控炎症在内皮损伤的作用引起广泛的重视，其确切机制亟待阐明。前期证实贵州地产特色民族药——艳山姜挥发油（EOFAZ）对高糖诱导内皮细胞损伤具有显著的保护作用，其机制与抑制炎症因子表达相关。本研究以EOFAZ为研究对象，建立细胞与动物实验模型，采用激动剂与拮抗剂及基因转染技术，探索调控PPAR-γ/NF-κB的关键分子，为糖尿病内皮损伤防治提供新的靶位与理论指导，阐明EOFAZ防治糖尿病内皮功能障碍的作用及机制，证实民族药新药理作用及作用机制，为其深层次研究奠定理论指导和实验基础。.本项目建立高糖诱导血管内皮细胞损伤模型、高糖高脂饲料+ STZ 建立 II 型糖尿病模型，采取基因敲降及药理学激动剂与抑制剂，在分子、细胞水平，阐明糖尿病血管内皮损伤PPAR-γ/NF-κB调控的关键机制，尤其是围绕NF-κB活化过程的相关信号——NF-κB自身表达、IκB与IKK的表达与调控，为临床糖尿病血管内皮损伤的防治提出新的理论指导和防治策略，为创新药物研制提供新的关键靶位；在细胞与整体动物模型证实EOFAZ通过调控PPAR-γ/NF-κB信号改善糖尿病血管内皮损伤的的新机制，为艳山姜的合理利用和深层次系统研究开发提供科学依据。项目执行期间发表标准本项目资助的论文11篇，其中SCI论文5篇，核心期刊论文6篇。培养博士研究生2名，硕士研究生生10名。获得发明专利2项，申请发明专利1项。项目负责人获得贵州省核心专家、贵州省优秀科技工作者、贵州省优秀博士研究生导师、贵州省普通本科高校“金师”。