急性高血糖与内皮功能紊乱长城课件.ppt

血管内皮 血管内皮功能受损 高血压主要发病机制之一 早期发生动脉粥样硬化的风险增加 导致心肌缺血和冠状动脉疾病 糖尿病心血管并发症的发病机制 也可能是2型糖尿病的发病机制？ 慢性高血糖与内皮功能受损Chronic hyperglycaemia and endothelial dysfunction 急性高血糖与内皮依赖的血管舒张功能受损 体外： 血管舒张功能的研究证实： 大鼠或家兔的动脉在高糖条件下孵育，可以抑制NO介导的血管舒张功能。 Experimental design Evidence suggests that intermittent high glucose levels induce high concentrations of ICAM and VCAM in endothelial cells – both are involved in atherogenesis 急性高血糖体内研究（个体、群体水平）  Methods Forearm blood flow measured by ultrasonography combining B-mode imaging and Doppler beams or blood pressure monitoring Stimuli used （诱导急性高血糖状态） Hyperglycaemic glucose clamp Standard oral 75 g glucose loading Endothelium-dependent vasodilators Antioxidants （谷胱甘肽） Blood samples taken to measure: levels of TBARS (脂质氧化产物) content of prothrombin fragments 1 + 2 (F1 + 2) circulating levels of soluble ICAM 急性高血糖诱导内皮功能受损 (I) 急性高血糖诱导内皮功能受损 (II) 急性高血糖对人体凝血酶原片段水平的影响 体内研究研究证实：正常人和2型糖尿病患者经OGTT负荷后，血清凝血酶原片段水平增高，应用抗氧化剂或谷胱甘肽后可恢复正常。 提示：急性高血糖通过氧化应激途径，诱导凝血酶原活性增加。 Prothrombin fragment (F1 + 2) variations during OGTT in (A) type 2 diabetes and (B) normal subjects Circulating ICAM-1 and plasma glucose in (A) patients with type 2 diabetes and (B) normal subjects Evidence has been shown to suggest that acute high glucose levels result in: Inhibition of vasodilation in blood vessels in vitro and in vivo – this effect is reversed by the presence of L-arginine or antioxidants Endothelial cell apoptosis in vitro Inhibition of flow-mediated vasodilation in vivo in normal, IGT and diabetic individuals High concentrations of prothrombin fragments and ICAM in vitro and in vivo The damaging effects induced by acute hyperglycaemia are probably a result of free radical production 小 结 ? 体外和体内研究均证实：进行高血糖可以诱导血管内 皮损伤； ? 血管内皮损伤在早期糖尿病心血管病发病机制中 起着重要作用； ? 抗氧化剂可以纠正急性高血糖诱导的内皮功能损伤； ? 提示：急性高血糖通过氧化应激途径诱导内皮功能受损， 抗氧化应激治疗对血管内皮具有保护作用。 Glucose utilisation and generation of oxidants in the endothelial cell 中药复合制剂抗高葡萄糖诱导的内皮细胞损伤研究 高糖抑制内皮细胞生长 中药和NAC预防高