吡格列酮抑制载脂蛋白E基因敲除小鼠主动脉粥样硬化病变进展及可能机制

目的观察吡格列酮对高脂饲料喂养的载脂蛋白E基因敲除小鼠主动脉粥样硬化病变及其血浆脂联素水平的影响,以探讨噻唑烷二酮类药物抗动脉粥样硬化作用及其可能的机制。方法取9只17周龄雄性C57BL/6J小鼠普通饲料喂养4周为对照组;另取31只同周龄雄性载脂蛋白E基因敲除小鼠随机分成三组给予高脂饲料喂养4周,其中模型组(n=10)单用高脂饲料喂养,低剂量治疗组(n=10)经胃管给予吡格列酮10 mg/(kg.d),高剂量治疗组(n=11)经胃管给予吡格列酮20 mg/(kg.d)。所有试验小鼠均观察其主动脉粥样硬化病变及血脂、血浆脂联素水平。结果与对照组比,所有载脂蛋白E基因敲除小鼠血脂水平显著升高并伴有主动脉内膜明显增厚及内膜下粥样斑块形成;与对照组(18.96±4.89μg/L)比,模型组血浆脂联素水平(12.41±3.84μg/L)显著下降,而两治疗组脂联素水平(18.78±7.24和24.00±4.71μg/L)比模型组显著升高,主动脉粥样硬化病变却减轻,且这种变化在高剂量治疗组更明显。结论吡格列酮抑制载脂蛋白E基因敲除小鼠主动脉粥样硬化病变的进展可能与其提高血浆脂联素水平有关。

Anti-atherosclerotic Effects and Possible Mechanism of Pioglitazone on Apolipoprotein E Knockout Mice

Aim To investigate the change of aortic atherosclerosis and plasma adiponectin of apolipoprotein E knockout(ApoE-/-) mouse treated with piogitazone. Methods 9 male mice of C57BL,17 weeks aged,were fed with common food for 4 weeks as simple control group.In addition,31 same age male mice of ApoE-/-were fed with high fatty food for setting up atherosclerosis animal models,and these mice were divided into three groups at random including:model group only receiving high fatty food for 4 weeks,low-dose treated group receiving piogitazone administered via gastric tube at 10 mg/(kg·d) for consecutive 4 weeks,high-dose treated group receiving piogitazone administered via gastric tube at 20 mg/(kg·d) for consecutive 4 weeks.The change of aortic atherosclerosis and levels of plasma adiponectin,plasma lipids of all mice were analyzed. Results The plasma levels of total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol in all ApoE-/-mice were significantly increased than those in control group(P<0.01);The plasma adiponectin level in model group was significantly decreased than that of control group,but the plasma adiponectin was elevated and the lesions of aortic atherosclerosis were inhibited in two treated groups,moreover,these change were more significant in highdose treated group(P<0.05). Conclusions Pioglitazone inhibits aortic atherosclerosis in ApoE-/-mice,and these effects may be related to plasma adiponectin level increasing.