抵挡汤早期干预调节2型糖尿病大血管病变细胞外基质合成分解平衡机制研究

Diabetic macrovascular complications are the leading cause of death and disability, whereas di dang tang can protect vascular endothelium in type 2 diabetic patients with macrovascular complications and its early intervention can significantly reduce the inflammation reaction of the large vessels in type 2 diabetic rat. Results showed the main pathological change of posterior tibial artery was fibrosis in 86 type 2 diabetic cases with macrovascular complications. Inflammation reaction, as the initiator of macrovascular complications, can be effectively reduced by di dang tang in T2DM rat. We hypothesized that di dang tang could decrease or delay the onset of type 2 diabetic macrovascular complications through adjusting the balance of degradation and synthesis of extracellular matrix and reducing fibrosis in the early stage. Taking animal and cellular models as the study subjects, TGF-βand Smad signal transduction pathways as the pointcut, a series of methods like ELISA, real-time PCR, immunofluorescence double staining technique and Western Blot were used. This study discussed the effects of early intervention of di dang tang on the balance of extracellular matrix and investigated its regulatory mechanism and also provided theory basis for preventive treatment of disease in Traditional Chinese Medicine.

糖尿病大血管病变是糖尿病患者致死、致残的主要因素，抵挡汤有保护2型糖尿病大血管病变患者血管内皮的作用,抵挡汤早期干预可以有效降低2型糖尿病大鼠大血管病变的炎症反应；同时对86例T2DM大血管病变患者的胫后动脉病理学观察发现其病理改变以纤维化为主；抵挡汤可以有效降低2型糖尿病大鼠大血管病变的启动因素-炎症反应，因此提出抵挡汤早期干预通过调节细胞外基质合成、分解平衡而减少纤维化发生，而起到减少或延缓2型糖尿病大血管病变发生的假说。本课题以动物和细胞模型为对象，以TGF-β信号转导通路和Smad信号通路为切入点，应用ELISA、实时荧光定量PCR、免疫荧光双染技术、Western-Blot等方法，探讨抵挡汤早期干预对2型糖尿病大鼠大血管的ECM合成、分解平衡的调节机制，为中医"治未病"理论提供依据。

前期工作基础证实糖尿病大血管病变病理学改变以纤维化为主，但机理不明。而抵挡汤早期干预可有效降低2型糖尿病大鼠主动脉损伤的重要启动因素炎症反应，同时有保护2型糖尿病患者大血管内皮作用，本课题证实抵挡汤早期干预可通过调节MMPs/TIMPs表达平衡、抑制AngⅡ、TGF-β/Smads信号通路及CTGF的表达，调节血管病变细胞外基质合成、分解平衡，最终减少大血管纤维化的发生。糖尿病大血管病变是糖尿病患者致残、致死的主要原因，本课题明确了抵挡汤防治2型糖尿病大血管病变的具体机制，为临床提供2型糖尿病大血管病变的防治提供新思路，为中医“治未病”理论提供依据。