Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Vasc Endovasc Surg. 2010 Dec;40(6):796-803. doi: 10.1016/j.ejvs.2010.07.009. Epub 2010 Aug 12.
To identify the optimal mouse model for hind limb ischaemia, which offers a therapeutic window that is large enough to detect improvements of blood flow recovery, for example, using cell therapies.
Different surgical approaches were performed: single coagulation of femoral and iliac artery, total excision of femoral artery and double coagulation of femoral and iliac artery. Blood flow restoration was analysed with laser Doppler perfusion imaging (LDPI). Immuno-histochemical stainings, angiography and micro-computed tomography (CT) scans were performed for visualisation of collaterals in the mouse.
Significant differences in flow restoration were observed depending on the surgical procedure. After single coagulation, blood flow already restored 100% in 7 days, in contrast to a significant delayed flow restoration after double coagulation (54% after 28 days, P<0.001). After total excision, blood flow was 100% recovered within 28 days. Compared with total excision, double coagulation displayed more pronounced corkscrew phenotype of the vessels typical for collateral arteries on angiographs.
The extent of the arterial injury is associated with different patterns of perfusion restoration. The double coagulation mouse model is, in our hands, the best model for studying new therapeutic approaches as it offers a therapeutic window in which improvements can be monitored efficiently.
确定一种最佳的用于后肢缺血的小鼠模型,该模型提供的治疗窗口足够大,可用于检测血流恢复的改善,例如使用细胞治疗。
进行了不同的手术方法:股动脉和髂动脉单次凝闭、股动脉全切和股动脉及髂动脉双凝闭。使用激光多普勒灌注成像(LDPI)分析血流恢复情况。进行免疫组织化学染色、血管造影和微计算机断层扫描(CT)扫描,以可视化小鼠中的侧支血管。
根据手术过程,观察到血流恢复存在显著差异。在单次凝闭后,血流在 7 天内已恢复 100%,而双凝闭后血流恢复显著延迟(28 天后为 54%,P<0.001)。在股动脉全切后,血流在 28 天内完全恢复。与股动脉全切相比,双凝闭后血管的螺旋状表现更为明显,这是侧支动脉的典型表现。
动脉损伤的程度与不同的灌注恢复模式相关。在我们的手中,双凝闭小鼠模型是研究新治疗方法的最佳模型,因为它提供了一个治疗窗口,可以有效地监测改善情况。