动脉粥样硬化（AS）是糖尿病心血管并发症的病理基础，内皮细胞功能障碍是AS的始动环节。申请人发现线粒体分裂-融合动态失衡是糖尿病血管内皮功能障碍的诱因。中医认为“气虚血瘀”是糖尿病AS的主要病机，“益气活血”经典名方补阳还五汤治疗糖尿病AS疗效显著，但其机制尚待阐明。前期研究发现：该方抑制线粒体分裂及其关键调控蛋白Drp1的表达，改善内皮功能和延缓AS的形成。本课题拟在ApoE-/-小鼠和内皮细胞，采用多环节抑制或增加Drp1活性，明确该方基于调控线粒体分裂治疗糖尿病AS的新机制；通过拮抗和激动AMPK及自噬通路，阐明其调控Drp1表达及线粒体动态平衡的新靶点；阐释糖尿病AS从能量代谢调节器AMPK失活、线粒体功能障碍（气虚）导致血管内皮功能障碍、血流减缓（血瘀）的病机及该病“本虚标实”的病理特点，揭示该方发挥“益气活血”功效的生物学基础，利于益气活血法科学内涵的理解及中医气血理论的提升。

Atherosclerosis (AS) is the pathogenesis of diabetic cardiovascular complications, and endothelial dysfunction is the early step of AS. We reported that the disruption of mitochondrial fission-fusion dynamics triggers endothelial dysfunction in diabetes mellitus. In Traditional Chinese Medicine, "qi deficiency and blood stasis" is the main pathogenesis of diabetic AS. Buyang Huanwu decoction, a well-known traditional Chinese medicine prescription for supplying Qi and activating blood circulation, has significantly beneficial effect on treatment of diabetic AS. However, the underlying mechanism remains to be elucidated. The preliminary data demonstrated that Buyanghuanwu decoction inhibits mitochondrial fission and the key regulatory protein Drp1, and improves endothelial function as well as prevents the development of AS in diabetes mellitus. Therefore, this study aims to clarify the mechanism of Buyanghuanwu decoction in preventing diabetic AS via activating or inhibiting Drp1, and identify the molecular target of Buyanghuanwu decoction on Drp1 expression and mitochondrial fission by antagonizing and agonizing AMPK and autophagy pathway. The study explains the pathogenesis of diabetic AS that AMPK inactivation, as an energy metabolism regulator, and mitochondrial dysfunction (Qi deficiency) results in endothelial dysfunction and blood flow slow (Blood stasis ), and the characteristics of diabetic AS as “deficiency in origin and excess in superficiality”. The outcome of the study identifies the biological basis of the Buyanghuanwu decoction, enriches the connotation of “supplement Qi and activating Blood Circulation” and “Qi and Blood theory” of traditional Chinese medicine.