叶酸对高脂血症状态下缺血性血管新生的改善作用

Folate Restores Hypercholesterolemia-Related Impairment of Angiogenesis in Respone to Ischemia

目的检验口服叶酸能否改善高脂血症(HC)对缺血组织血管新生的抑制。方法雄性大鼠54只,随机分为对照组、HC组和HC+叶酸(F)组,每组18只。用手术的方法结扎大鼠左侧股动、静脉,观察其缺血下肢的血管新生情况。结果术后14 d血流仪分析显示:HC组缺血/非缺血下肢血流比值较对照组明显下降;毛细血管评分记数和毛细血管密度均表明HC组明显低于对照组;而HC+F组均较HC组明显升高;上述结果与组织中一氧化氮(NO)和环磷酸鸟酸(cGMP)含量变化有关。结论HC对下肢缺血性血管新生和侧枝血管的建立有明显的抑制作用,口服叶酸能够使被抑制的缺血性血管新生得以恢复。

Objective To examine whether oral folate supplementation would rescue hypercholesterolemia （HC）- related impairment of angiogenesis in response to tissue ischemia. Methods Fifty-four male Sprague-Dawley rats were randomly divided into 3 groups （n = 18 in each group） ： control group, normal diet; H C group, 2% cholesterol diet; and HC ＋ folate（F） group, 2% cholesterol diet supplemented with oral folate. The left femoral artery and vein were excised, and angiogenesis in the ischemic limb was evaluated for 4 weeks.. Results Fourteen clays after operation, laser Doppler blood flow （LDBF） analysis showed a significantly lower ischemic/normal hindlimb ratio in the HC group than in the control group, and angiographic and histological analysis in the ischemic limb revealed a significantly lower angiographic score and capillary density in the HC group than in the control group. However, the LDBF ratio, angiographic score and capillary density were significantly restored in the HC ＋ F group. All the above observations were associated with the changes in tissue NOx and cGMP contents. Conclusion Angiogenesis and collateral vessel formation in response to hindlimb ischemia could be inhibited by HC, and oral folate supplementation could restore the HC-related impairment of angiogenesis.