抵挡汤早期干预对糖尿病大血管病变血管内皮防御功能的作用机制研究

Diabetic macrovascular disease is the main reason for diabetic patients to the death and disability, and a large number of studies have shown that: Intensive glucose control can not delay the occurrence of the diabetic macrovascular disease. We have found in the study (the National Natural Science Foundation of China- - - - 30973573) that: The early application of Didang Decoction had the effects of reducing the expression of MCP-1, CD68 and E- selectin, influencing the activation, migration and adhesion of the monocyte / macrophage, and delaying the process and extent of the diabetic macrovascular disease. Defensive function of the vascular endothelium is its main function. Accordingly, we proposed the hypothesis that it is the key for enhancing the vascular endothelial defensive function to reduce the occurrence of the type 2 diabetic macrovascular disease through regulating the energy metabolism of the vascular endothelial cells and improving their functional status, and regulating vascular endothelial permeability and cell junction signaling pathway. In this study, we aim the type 2 diabetic rats and human umbilical vein endothelial cells as the object, and explore the protective effects of the early intervention with Didang Decoction on the defensive function of the diabetic macrovascular endothelium from the aspects of the cellular energy metabolism by using the transmission electron microscopy, confocal laser scanning, real-time fluorescence quantitative PCR, Western-Blot, and other methods.We look forward to provide a theoretic basis for the theory " preventive treatment of disease " and "righteousness existing, evil not invading" in traditional Chinese medicine through our studies.

糖尿病大血管病变是糖尿病患者致死、致残的主要原因，大量研究表明：强化血糖控制不能延缓糖尿病大血管病变的发生。在前期主持国家自然科学基金(30973573)中发现：早期应用抵挡汤能够降低MCP-1、CD68、E-选择素的表达，影响单核/巨噬细胞活化、迁移、黏附，延缓糖尿病大血管病变的进程及程度。血管内皮的防御功能是其最主要功能,据此提出调节血管内皮细胞的能量代谢，改善其功能状态、调节血管内皮通透性及细胞连接信号转导通路而增强血管内皮防御功能是减少2型糖尿病大血管病变的发生的关键假说。本研究以2型糖尿病大鼠和人脐静脉血管内皮细胞为研究对象，应用透射电镜、激光共聚焦、实时荧光定量PCR、Western-Blot等方法，从细胞的能量代谢角度探讨抵挡汤早期干预对糖尿病大血管内皮的防御功能的保护作用。为探索中医"治未病""正气存内,邪不可干"理论提供依据。

糖尿病大血管病变是糖尿病患者致死、致残的主要因素。血管内皮损伤是导致糖尿病大血管病变的发生重要因素。因此课题组开展了抵挡汤对糖尿病大鼠和人脐静脉血管内皮细胞的实验研究。通过对2型糖尿病大鼠大血管病变及人脐静脉血管内皮细胞功能的实验研究表明：抵挡汤早期干预可通过调控AMP/ATP值，增加AMPKα1活性，抑制Caspase-3活性，升高Bcl-2活性；可降低ROS水平，下调AIF、Apaf-1、Caspase-3基因表达水平，从而延缓糖尿病大血管并发症的发生发展。