首页> 外文期刊>Journal of vascular surgery >Recovery from hind limb ischemia is less effective in type 2 than in type 1 diabetic mice: roles of endothelial nitric oxide synthase and endothelial progenitor cells.
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Recovery from hind limb ischemia is less effective in type 2 than in type 1 diabetic mice: roles of endothelial nitric oxide synthase and endothelial progenitor cells.

机译:从2型糖尿病小鼠中恢复后肢缺血效果不如1型糖尿病小鼠:内皮型一氧化氮合酶和内皮祖细胞的作用。

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OBJECTIVE: We sought to directly compare the effects of type 1 and type 2 diabetes on postischemic neovascularization and evaluate the mechanisms underlying differences between these groups. We tested the hypothesis that type 2 diabetic mice have a greater reduction in endothelial nitric oxide synthase (eNOS) expression, a greater increase in oxidative stress, and reduced arteriogenesis and angiogenesis, resulting in less complete blood flow recovery than type 1 diabetic mice after induction of hind limb ischemia. METHODS: Hind limb ischemia was generated by femoral artery excision in streptozotocin-treated mice (model of type 1 diabetes), in Lepr(db/db) mice (model of type 2 diabetes), and in control (C57BL/6) mice. Dependent variables included eNOS expression and markers of arteriogenesis, angiogenesis, and oxidative stress. RESULTS: Postischemia recovery of hind limb perfusion was significantly less in type 2 than in type 1 diabetic mice; however, neither group demonstrated a significant increase in collateral artery diameter or collateral artery angioscore in the ischemic hind limb. The capillary/myofiber ratio in the gastrocnemius muscle decreased in response to ischemia in control or type 1 diabetic mice but remained the same in type 2 diabetic mice. Gastrocnemius muscle eNOS expression was lower in type 1 and 2 diabetic mice than in control mice. This expression decreased after induction of ischemia in type 2 but not in type 1 diabetic mice. The percentage of endothelial progenitor cells (EPC) in the peripheral blood failed to increase in either diabetic group after induction of ischemia, whereas this variable significantly increased in the control group in response to ischemia. EPC eNOS expression decreased after induction of ischemia in type 1 but not in type 2 diabetic mice. EPC nitrotyrosine accumulation increased after induction of ischemia in type 2 but not in type 1 diabetic mice. EPC migration in response to vascular endothelial growth factor was reduced in type 1 and type 2 diabetic mice vs control mice. EPC incorporation into tubular structures was less effective in type 2 diabetic mice. Extensive fatty infiltration was present in ischemic muscle of type 2 but not in type 1 diabetic mice. CONCLUSION: Type 2 diabetic mice displayed a significantly less effective response to hind limb ischemia than type 1 diabetic mice.
机译:目的:我们试图直接比较1型和2型糖尿病对缺血后新生血管形成的影响,并评估这些组之间差异的潜在机制。我们测试了以下假设,即2型糖尿病小鼠的内皮一氧化氮合酶(eNOS)表达降低更多,氧化应激增加更大,动脉生成和血管生成减少,导致诱导后的血流恢复不如1型糖尿病小鼠。后肢缺血。方法:在经链脲佐菌素治疗的小鼠(1型糖尿病模型),Lepr(db / db)小鼠(2型糖尿病模型)和对照组(C57BL / 6)小鼠中,股动脉切除后肢缺血。因变量包括eNOS表达和动脉生成,血管生成和氧化应激的标志物。结果:2型糖尿病小鼠的后肢缺血后恢复明显低于1型糖尿病小鼠。然而,两组均未显示缺血后肢的侧支动脉直径或侧支血管明显增加。在对照组或1型糖尿病小鼠中,腓肠肌中的毛细血管/肌纤维比率响应缺血而降低,但在2型糖尿病小鼠中保持不变。 1型和2型糖尿病小鼠的腓肠肌eNOS表达低于对照组小鼠。在2型缺血小鼠中,这种表达在诱导缺血后降低,但在1型糖尿病小鼠中没有降低。在任何一个糖尿病组中,诱导缺血后,外周血中内皮祖细胞(EPC)的百分比均未增加,而对照组中,响应缺血后,该变量显着增加。 EPC eNOS表达在缺血诱导后在1型糖尿病小鼠中降低,但在2型糖尿病小鼠中没有降低。 EPC硝基酪氨酸的积累在缺血诱导后在2型糖尿病小鼠中增加,但在1型糖尿病小鼠中没有增加。 1型和2型糖尿病小鼠与对照组相比,EPC对血管内皮生长因子的迁移减少。 EPC并入肾小管结构在2型糖尿病小鼠中效果较差。 2型缺血性肌肉中存在大量脂肪浸润,但1型糖尿病小鼠中则不存在。结论:2型糖尿病小鼠对后肢缺血的有效反应明显低于1型糖尿病小鼠。

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