非胰岛素依赖型糖尿病小鼠对缺血刺激的反应及其机制研究

目的研究在非胰岛素依赖型糖尿病状态下,小鼠肢体对缺血刺激的血管生成反应,并探讨其发生机制。方法雄性C57BL／6小鼠40只,分别以常规饲料（对照组20只）和高脂肪饲料（糖尿病组20只）喂养。12周后,创建小鼠下肢动脉缺血模型,应用激光多普勒扫描仪记录肢体血流恢复情况。术后4周处死小鼠,取下肢肌肉组织行组织病理学检查,CD31染色,评价血管密度;取正常下肢肌肉组织分别行ELISA和Western Blot检测血管内皮生长因子（VEGF）及其下游因子AKT的表达状况,行逆转录聚合酶链反应检测VEGF受体的表达情况。结果非胰岛素依赖型糖尿病鼠肢体缺血后其自身恢复和新生血管密度明显低于正常对照组小鼠;肌肉组织中VEGF浓度明显高于对照组,而VEGF受体表达差异却无统计学意义。肌肉组织中PAKT／AKT比值明显低于对照组。结论非胰岛素依赖型糖尿病肢体对缺血刺激的反应明显减弱,这一现象可能与VEGF信号传导通路功能不全有关。

Spontaneous response and mechanism to ischemia in diabetic mouse

Objective To investigate the spontaneous response and its mechanism of type 2 diabetes mouse to surgical induced hind limb ischemia. Methods Forty mice were randomly divided into two groups, one was fed with normal chow, and another was fed with high fat diet. Twelve weeks later, mice were surgical induced to hind limb ischemia. Blood flow was monitored. Four weeks later, mice were sacrificed and muscle tissues were harvested for histological detection, Western Blot, ELISA and RT-PCR examination respectively. Results Spontaneous restoration of blood flow was significantly slow down in type 2 diabetic mice with lower level of vascular density in ischemic muscles. VEGF signaling pathway was impaired although the VEGF levels were increased in diabetes. Conclusions The spontaneous response to ischemia was attenuated with an abnormal reaction of VEGF signaling pathway in the setting of type 2 diabetes mellitus.