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Journal of ZheJiang University(Medical Science)  2014, Vol. 43 Issue (3): 293-298    DOI: 10.3785/j.issn.10089292.2014.05.006
    
Effect of simvastatin on atherosclerosis and central aortic pressure in ApoE gene knockout mice
LIU Ming, JIN Yu-hong, LI Tiao-hong, SHI Lin-hui, ZHU Bao-qi
Ningbo Medical Treatment Center Lihuili Hospital, Ningbo 315000, China
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Abstract  

Objective: To investigate the effects of simvastatin on atherosclerosis and central aortic pressure in ApoEknockout (ApoE-/-) mice. Methods: Ten 5weekold male ApoE-/- mice and 5 C57 mice were fed with highlipid diet for 3 weeks, and then C57 mice (WT group) and 5 ApoE-/- mice (ApoE-/- group) were given 1% carboxymethyl cellulose solution (8 ml·kg-1·d-1), and another 5 ApoE-/- mice (ApoE-/-/S group) were given simvastatin solution (50 mg·kg-1·d-1) by gavege for 3 weeks. The areas of atherosclerotic lesion in aortic root, central aortic pressure and serum lipid levels were examined. Results: No atherosclerotic plaques were observed in WT group. Compared with ApoE-/- group, simvastatin significantly decreased atherosclerotic lesion area in aortic root (89 81805±16 98093 μm2 vs 34 93701±13 28065 μm2, P<005). The systolic pressure (SP), mean arterial pressure (MAP), pulse pressure (PP) and diastolic pressure (DP) of central aortic pressure were significantly increased in ApoE-/- group compared with those in WT group (P<005). Compared to ApoE-/- group, the SP, MAP and PP of central aortic pressure were significantly reduced in ApoE-/-/S group (P<005). SP and MAP of central aortic pressure were positively correlated with atherosclerotic lesion area (SP: r=07152, P=00461; PP: r=07594, P=00288). Compared with WT group, serum triglyceride, total cholesterol and lowdensity lipoprotein levels were markedly increased in ApoE-/- group (P<005). Serum highdensity lipoprotein level was decreased in ApoE-/- group compared with WT group. No differences in serum triglyceride, total cholesterol, lowdensity lipoprotein and highdensity lipoprotein levels were found between ApoE-/- group and ApoE-/-/S group. Conclusion: Simvastatin can attenuate atherosclerosis of aorta in ApoE-/- mice, which is associated with the reduced central aortic systolic pressure but not with the serum lipids levels.



Key wordsAtherosclerosis/drug therapy      Blood pressure/drug effects      Blood pressure/physiology      Disease models, animal     
Received: 26 September 2013     
Corresponding Authors: ZHU Baoqi, Email: zhubaoqi_nb@163.com   
Cite this article:

LIU Ming, JIN Yu-hong, LI Tiao-hong, SHI Lin-hui, ZHU Bao-qi . Effect of simvastatin on atherosclerosis and central aortic pressure in ApoE gene knockout mice. Journal of ZheJiang University(Medical Science), 2014, 43(3): 293-298.

URL:

http://www.zjujournals.com/xueshu/med/10.3785/j.issn.10089292.2014.05.006     OR     http://www.zjujournals.com/xueshu/med/Y2014/V43/I3/293


辛伐他汀对载脂蛋白E基因敲除小鼠动脉粥样硬化和中心动脉压的影响

目的:探讨辛伐他汀对载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化和中心动脉压的影响及后两者的相关性。方法:5周龄雄性ApoE-/-小鼠和C57小鼠,分为野生组、ApoE-/-组和辛伐他汀组,予以高脂饮食喂养。辛伐他汀组8周龄开始给予辛伐他汀(50 mg·kg-1·d-1),干预3周后测量主动脉根部动脉粥样硬化斑块面积、中心动脉压及血脂水平。结果:野生组未形成动脉粥样硬化斑块;与ApoE-/-组比较,辛伐他汀组ApoE-/-小鼠动脉粥样硬化斑块面积减小[(89 81805±16 98093) μm2比(34 93701±13 28065) μm2,P<005]。同时,ApoE-/-组中心动脉压的收缩压、舒张压、平均动脉压和脉压均明显高于野生组(均P<005);与ApoE-/-组相比,辛伐他汀组ApoE-/-小鼠中心动脉压的收缩压、平均动脉压和脉压均降低(均P<005),舒张压降低无统计学意义(P>005)。此外,中心动脉压的收缩压(n=8,r=07152,P=00461)和脉压(n=8,r=07594,P=00288)与动脉粥样硬化斑块面积成正相关。与野生组相比,ApoE-/-组血清三酰甘油、总胆固醇与低密度脂蛋白水平均升高,而高密度脂蛋白水平降低(P<005);辛伐他汀组血清三酰甘油、总胆固醇、低密度脂蛋白、高密度脂蛋白水平与ApoE-/-组差异无统计学意义(P>005)。结论:辛伐他汀通过非降脂途径降低ApoE-/-小鼠动脉粥样硬化斑块面积和中心动脉压,且其对中心动脉压的调节可能在抑制动脉粥样硬化过程中发挥作用。


关键词: 动脉粥样硬化/药物疗法;动脉粥样硬化/病理学作用,  血压/生理学;疾病模型, 动物 
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