基于HIF-1a调控血管新生研究糖尿病阴证创面“阳虚腐生”病机及温阳生肌膏的作用

血管新生困难是糖尿病阴证创面难愈的重要问题，HIF-1α可调控血管新生下游靶基因，与线粒体能量代谢及炎症密切相关，并受多因素影响，是调控血管新生的关键环节。前期研究表明：（1）温阳生肌膏可提高小鼠创面线粒体代谢、糖有氧氧化相关酶的乙酰化水平；（2）温阳生肌膏在临床上有效促进糖尿病阴证创面愈合，也可促糖尿病阴证大鼠创面血管新生。但其机制不明确。因此，本项目拟采用Ⅱ型糖尿病大鼠背部全层皮肤缺损及血管内皮细胞高糖缺氧模型，以HIF-1α为切入点，研究温阳生肌膏促血管新生对糖尿病阴证创面愈合作用的细胞分子机制，明确温阳生肌膏“温阳”与HIF-1α血管新生相关信号、“糖-氧-能-效”中糖代谢相关酶活性及线粒体能量代谢的关系，“祛腐”与MGO、AGEs、ROS、炎症因子等有害物质引起的炎症反应的关系，从而揭示糖尿病阴证创面阳虚腐生中医病机的科学内涵，为其临床合理应用和进一步开发提供科学依据。

Angiogenesis difficulty is an important problem in the wound of diabetic yin syndrome. HIF-1α can regulate the target gene of angiogenesis, which is closely related to mitochondrial energy metabolism and inflammation, and is affected by many factors, which is the key link of regulating angiogenesis. Previous studies have shown that :(1) Wenyangshengji ointment can improve the acetylation level of mitochondrial metabolism, sugar and aerobic oxidation-related enzymes in the wound surface of mice ;(2) Wenyangshengji ointment can effectively promote the wound healing of diabetic yin syndrome and promote angiogenesis in the wound of diabetic yin syndrome rats.But its mechanism is unclear.Therefore, this project intends to study the cellular molecular mechanism of the effect of Wenyangshengji ointment on wound healing of diabetic yin syndrome by using HIF-1α as the entry point to study the whole skin defect and high glucose hypoxia model of vascular endothelial cells in type II diabetic rats. provide scientific basis for its rational clinical application and further development.