泽泻饮通过调节ApoE-/-小鼠胆固醇代谢改善动脉粥样硬化
The Improvement of Atherosclerosis from Zexieyin by Regulating Cholesterol Metabolism in the Apolipoprotein E-Deficient Mice
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摘要: 目的 探讨泽泻饮对ApoE-/-小鼠动脉粥样硬化模型动脉管腔病变程度及血脂水平的影响及其作用机制。方法 将40只雄性8周龄ApoE-/-小鼠随机分为高脂饮食组、泽泻饮低剂量组(LZXY)、泽泻饮高剂量组(HZXY)以及阿托伐他汀组(Ato)作为阳性对照组,以10只C57BL/J6小鼠为空白对照组。测定血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)与高密度脂蛋白(HDL-C)的水平,油红O染色观察主动脉弓根部的病变程度,Western blot法分别检测小鼠肝脏组织中LXRα、CYP7A1、ABCG5和ABCG8蛋白表达水平与小肠组织中LXRα、NPC1L1、SREBP2、ABCG5与ABCG8蛋白表达水平。结果 与高脂饮食组相比,泽泻饮可明显改善小鼠血脂水平,改善动脉粥样硬化病变,且具有剂量依赖性。在小鼠肝脏组织中,泽泻饮显著上调了LXRα、CYP7A1、ABCG5、ABCG8的表达。在小鼠小肠组织中泽泻饮提高了LXRα、ABCG5、ABCG8的表达水平,并抑制了NPC1L1与SREBP2的表达。结论 泽泻饮可以有效抑制动脉粥样硬化的进展,改善血脂水平,其作用机制可能与抑制胆固醇吸收、促进胆固醇排泄有关。Abstract: OBJECTIVE To explore the effect and mechanism of Zexieyin on the degree of artery lumen lesion and blood lipid level in ApoE-/- mice model of atherosclerosis. METHODS Male ApoE-/- mice were randomly divided into four groups: the high-fat diet group (HFD), the low-dose ZXY group (LZXY), the high-dose ZXY group (HZXY) and the atorvastatin group (ATO) as positive control group. All the above groups were fed a high-fat diet. Another blank control group (Con) was administrated only a normal diet. The levels of the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) were measured. The lesions of aortic arch root were observed by Oil Red O staining. Western blot was used to detect the expression levels of Liver X receptor (LXR) α, cholesterol 7 alpha-hydroxylase A1 (CYP7A1), ATP-binding cassettes (ABC) G5 and ABCG8 in the liver, and LXR α, Niemann-pick C1-like 1 (NPC1L1), sterol regulatory element binding protein (SREBP-2), ABCG5 and ABCG8 in the small intestine. RESULTS The results showed that compared with the high-fat diet group, ZXY could significantly improve the blood lipid level and attenuate the atherosclerotic lesions in a dose-dependent manner. In the liver of mice, the expression levels of LXR-α, CYP7A1, ABCG5 and ABCG8 were significantly increased by ZXY. In the small intestine of mice, ZXY increased the expression levels of LXR-α, ABCG5 and ABCG8, and inhibited the expression levels of NPC1L1 and SREBP2. CONCLUSION ZXY can effectively inhibit the progression of AS and alleviate the blood lipid level, and its mechanism might be related to the inhibition of cholesterol absorption and the promotion of cholesterol excretion, which indicates that ZXY has potential value for prevention and treatment of AS.
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Key words:
- Zexieyin /
- atherosclerosis /
- cholesterol metabolism
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