茶黄素-3,3'-O-双没食子酸酯对糖尿病大鼠血管内皮损伤及炎症反应的保护作用

探讨茶黄素-3,3'-O-双没食子酸酯（TFDG）对糖尿病大鼠血管内皮损伤及炎症反应的保护作用及相关机制。以高脂饲料喂养加链脲佐菌素注射制造糖尿病大鼠,将其分为模型组（CON）、5 mg·kg^-1和10 mg·kg^-1 TFDG干预组（TFDG5和TFDG10）,另取正常大鼠为对照组（NC）,分组处理8周,监测体重和空腹血糖变化,观察大鼠腹主动脉病理形态学变化,ELISA检测血浆IL-6、IL-1β和TNF-α水平,Western blot检测蛋白表达水平。结果表明,与CON组相比,TFDG干预对体重和血糖无显著影响,病理切片观察显示TFDG干预组大鼠腹主动脉组织损伤较CON组有所改善,同时TFDG干预组大鼠血浆炎症因子水平显著降低,血浆NO水平显著升高,腹主动脉组织MDA水平降低。进一步研究显示,TFDG下调了糖尿病大鼠腹主动脉组织NLRP3、caspase-1和IL-1β的表达,抑制NLRP3炎症通路激活。TFDG能够有效保护糖尿病大鼠血管内皮损伤并抑制炎症反应,其机制可能是通过下调NLRP3炎症通路实现的。

Effects of Theaflavin-3,3'-O-Digallate on Vascular Endothelial Injury and Inflammation in Rats with Diabetes Mellitus

To investigate the protective effect and mechanism of theaflavin-3,3'-O-digallate (TFDG) on vascular endothelial injury and inflammation in rats with diabetes mellitus, diabetic rats were made by high fat feed and streptozotocin injection and then divided into model group (CON), 5 mg·kg^-1 and 10 mg·kg^-1 TFDG intervention group (TFDG5 and TFDG10). The normal rats were taken as control group (NC). After 8 weeks of treatment, the pathological changes of abdominal aorta were observed. Plasma IL-6, IL-1β and TNF-α were detected by ELISA. The protein expression was detected by Western blot. Compared with CON, TFDG administration has no significant effects on body weight and fasting blood glucose. Pathological sections show that the injury of aorta tissue in TFDG group was improved compared with that in CON group. At the same time, the level of plasma inflammatory factors was significantly decreased, the level of plasma NO was significantly increased, and the level of MDA in aorta tissue was decreased in TFDG group. Further studies show that TFDG could down-regulate NLRP3, caspase-1 and IL-1β expressions in the aorta of diabetic rats. TFDG effectively protected vascular endothelial injury and inhibit inflammatory response in diabetic rats, and its mechanism might be through down-regulation of NLRP3 inflammatory pathway.