目的：探讨2-羟丙基-β-环糊精（2HP-β-CD）对小鼠下肢缺血模型的有效性及其作用机制，为治疗下肢缺血性疾病提供理论依据。方法将雄性C57BL/6小鼠随机分为4组：假手术组、空白对照组、0.1%牛血清白蛋白生理盐水组（正常对照组）及2HP-β-CD组，每组5只。建立小鼠下肢缺血模型。于术前及术后第1、3、5、7、10、14、21天采用激光多普勒血流仪观察血流恢复情况；于术后第21天处死动物取腓肠肌组织，进行病理学评价；采用免疫印迹法检测腓肠肌组织中Akt磷酸化表达水平。结果2HP-β-CD组血流恢复情况优于空白对照组及正常对照组（P<0.05），2HP-β-CD组缺血肌肉组织中毛细血管密度高于假手术组、空白对照组及正常对照组（P<0.05），2HP-β-CD组缺血肌肉组织Akt磷酸化蛋白表达情况高于假手术组、空白对照组及正常对照组（P<0.05），差异均具有统计学意义。结论2HP-β-CD可能是通过诱导Akt磷酸化促进小鼠下肢缺血模型的血管新生及血流恢复。%Objective To investigate the effect and the possible mechanism of (2-Hydroxypropyl)-β-cyclodex-trin (2HP-β-CD) on angiogenesis in ischemic hindlimbs of mice, to provide theoretical basis for treatment of ischemic disease of lower extremity. Method Theold male C57BL/6 mice were randomly divided into four groups: sham group, blank control group, 0.1% bovine serum albumin (BSA) saline group (normal control group) and 2HP-β-CD group, 5 mice for each group. Mice were subjected to surgical procedures to achieve uni-lateral hindlimb ischemia. The blood flow of ischemic (left) and contra-lateral non-ischemic (right) hindlimbs was measured with a laser Doppler blood flow (LDBF) analyzer before and day 1, day 3, day 5, day 7, day 10, day 14 and day 21 after operation. Ischemic tissue of calf muscle was excised for pathological evaluation and the phospho-Akt protein expression was detected by Western Blotting. Results Local administration of 2HP-β-CD significantly stimulated blood flow recovery compared with blank control group and normal control group (P<0.05), and dramatically stimulated angiogenesis with promotion of capillary density compared with sham operation group, blank control group and normal control group (P<0.05), and also remarkably increased the phospho-Akt protein expression compared with the other groups (P<0.05). Conclusion 2HP-β-CD can stimulate post-ischemic angiogenesis and blood flow recovery in a mouse ischemic hindlimb model probably through the upregulation of Akt phosphorylation.
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