Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
J Surg Res. 2012 Dec;178(2):1022-8. doi: 10.1016/j.jss.2012.04.067. Epub 2012 May 17.
The possible relation between menopause and the development of peripheral arterial disease, especially lower extremity disease, has not been fully studied. To explore this issue, we investigated whether estrogen deficiency affected neovascularization in a murine model of hindlimb ischemia.
Ischemia was surgically induced in one hindlimb of oophorectomized and control female BALB/c mice. Neovascularization in the ischemic hindlimbs was evaluated using laser Doppler blood flow analysis and capillary density analysis of the adductor muscle. The expression of endothelial nitric oxide synthase protein in the adductor muscle of the ischemic hindlimbs was assessed.
The plasma 17-β estradiol levels were significantly lower in the oophorectomized mice than in the control mice. The oophorectomized mice also had a significantly reduced blood perfusion index and capillary density on day 21 after the induction of hindlimb ischemia and significant suppression of endothelial nitric oxide synthase protein expression on day 3 after ischemia induction.
Estrogen deficiency attenuated neovascularization in a murine model of hindlimb ischemia. Impaired neovascularization in oophorectomized mice might correlate with a reduction in endothelial nitric oxide synthase expression caused by estrogen deficiency.
绝经与外周动脉疾病(尤其是下肢疾病)的发展之间可能存在关联,但这一问题尚未得到充分研究。为了探究这一问题,我们研究了雌激素缺乏是否会影响小鼠后肢缺血模型中的血管新生。
通过手术诱导去卵巢和对照雌性 BALB/c 小鼠的一只后肢缺血。采用激光多普勒血流分析和内收肌毛细血管密度分析评估缺血后肢的血管新生。评估缺血后肢内收肌中内皮型一氧化氮合酶蛋白的表达。
与对照组相比,去卵巢组小鼠的血浆 17-β 雌二醇水平显著降低。在诱导后肢缺血后第 21 天,去卵巢组的血流灌注指数和毛细血管密度显著降低,在缺血诱导后第 3 天,内皮型一氧化氮合酶蛋白表达显著受到抑制。
雌激素缺乏会减弱小鼠后肢缺血模型中的血管新生。去卵巢小鼠的血管新生受损可能与雌激素缺乏导致的内皮型一氧化氮合酶表达减少有关。