吡格列酮抗实验性小鼠主动脉粥样硬化的作用

Anti-atherosclerosis effect of pioglitazon on mouse

目的 观察停高脂喂饲或同时加吡格列酮干预对实验性小鼠主动脉壁脂质沉积及代谢紊乱的影响,探讨药物干预的时机及其血管保护作用的机制。方法 将经高脂喂养14周,血脂、血糖、胰岛素水平升高及主动脉内膜出现明显局灶性脂质沉积的成模型C57BL/6小鼠随机分为吡格列酮干预组(PIO组,予盐酸吡格列酮10 mg·kg-1·d-1灌胃)和动脉粥样硬化组(AS组)。分组后所有小鼠均改予普通饲料继续喂养8 周,前、后共22周。于实验第22周末再次测定血脂、血糖、胰岛素水平。采血同时取主动脉,采用油红“O”整体染色法观察其病理学变化。结果 与8周前相比,AS组血脂、血糖水平仅轻度下降(P>0.05),胰岛素水平无明显下降,主动脉血管处仍可见内膜有明显局灶性红染;PIO组血脂及胰岛素水平显著下降(P<0.05)、血糖轻度下降(P>0.05),主动脉血管分叉处内膜着色明显变淡。PIO组小鼠死亡数明显少于AS组。结论 经吡格列酮干预后,主动脉壁上沉积的脂质消退,吡格列酮这种血管保护的作用机制与其全面改善糖、脂代谢紊乱及胰岛素抵抗作用有关。

Objective To observe the influences of Pioglitazon for lipid deposition on aortic wall and metabolic disorder in experimental atherosclerotic mice.Methods The atherosclerotic mice of C57BL/6, model fed with cholesterol-rich diet for 14 weeks and developed local lipid deposition on the aortic wall with metabolic disorder, were divided into two groups: one received the ordinary diet together with Pioglitazon as the interventional group(PIO group, 10 mg·kg -1·d -1), the other received the ordinary diet only as the atherosclerotic control group(AS group). After another eight weeks, the metabolic indexe measurements were repeated again. The aortas were taken out and stained with oil red O to observe the pathologic changes. Results After eight weeks intervention with pioglitazone, both metabolic indexes and aortic wall lesions improved markedly, but none in the control group.Conclusion The aortic wall lipid deposition subsides after Pioglitazone intervention, probably due to improvement of metabolic disorder and insulin resistance.