摘要
目的观察黄酒是否可以通过黄酒多酚发挥对动脉粥样硬化斑块的抑制作用并探讨其可能机制。方法40只6周龄雄性低密度脂蛋白受体敲除(LDLR-/-)小鼠,高脂饲料喂养诱导形成动脉粥样硬化模型,随机分为高脂对照组、瑞舒伐他汀组、黄酒多酚10 mg/(kg·d)组、黄酒多酚30 mg/(kg·d)组和黄酒多酚50 mg/(kg·d)组,每组8只,分别予以无菌水、10 mg/(kg·d)瑞舒伐他汀和10、30、50 mg/(kg·d)黄酒多酚干预。16周后处死小鼠,检测血脂,观察胸腹主动脉粥样硬化情况,Western blot测定胸主动脉组织内基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、组织型基质金属蛋白酶抑制剂1(TIMP-1)及组织型基质金属蛋白酶抑制剂2(TIMP-2)的表达,明胶酶谱法测定主动脉弓动脉粥样硬化处MMP-2和MMP-9的活性。结果与高脂对照组相比,总胆固醇(TC)和低密度脂蛋白胆固醇(LDLC)在黄酒多酚组和瑞舒伐他汀组明显下降(P<0.01),甘油三酯(TG)在瑞舒伐他汀组明显下降(P<0.01),在黄酒多酚组差异不明显(P>0.05),在黄酒多酚组与瑞舒伐他汀组差异明显(P<0.05);5组间高密度脂蛋白胆固醇(HDLC)水平差异无统计学意义(P>0.05)。与高脂对照组相比,主动脉粥样硬化面积在瑞舒伐他汀组和黄酒多酚10、30、50 mg/(kg·d)组分别减少74.14%、18.51%、40.09%、38.42%(P<0.01),不同浓度黄酒多酚组主动脉粥样硬化面积与瑞舒伐他汀组比较差异显著(P<0.01)。黄酒多酚和瑞舒伐他汀均能明显抑制MMP-2、MMP-9的表达和活性(P<0.01),增强TIMP-1、TIMP-2的表达(P<0.01)。结论黄酒多酚具有类似瑞舒伐他汀的作用,能够调节血脂,在抑制MMP-2、MMP-9表达和活性的同时增强TIMP-1、TIMP-2的表达,减轻动脉粥样硬化斑块的形成,这可能是黄酒对心血管系统的保护机制之一。
Aim To study the possibility that yellow wine polyphenolic compounds improves the pathological changes of atherosclerosis in vivo. Methods Six weeks old LDL receptor knock out mice （n40） treated with high-fat diet were randomly allocated to five groups （8 rats in each group）： high fat group, rosuvastain intervention group,yellow wine polyphenolic compounds 10 mg/（kg·d） intervention group, yellow wine polyphenolic compounds 30 mg/（kg·d） intervention group, yellow wine polyphenolic compounds 50 mg/（kg·d） intervention group, they received by sterile water, 10 mg/（kg·d） rosuvastain and yellow wine polyphenolic compounds with dose of 10, 30, 50 mg/（kg·d） dissolved in sterile water, respectively. High fat diet were given to establish the mouse model with atherosclerosis. After 16 weeks, they were sacrificed. The levels of plasma lipids in serum were examined. The morphological changes of aorta artery were observed under microscope. The expression of matrix metalloproteinase-2 （MMP-2）, matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of matrix metalloproteinase-1 （TIMP-1）, tissue inhibitor of matrix metalloproteinase-2 （TIMP-2） were determined by Western blot. The activation of MMP-2, MMP-9 were determined by Gelatin Zymography. Results Compared to high fat group, the levels of total cholesterol （TC）, low density lipoprotein cholesterol （LDLC） and triglyceride （TG） were significantly decreased in rosuvastain intervention group （P〈0.01） except for TG, plasma TC and LDLC levels were significantly decreased in yellow wine polyphenolic intervention compounds groups （P〈0.01）. The levels of plasma TC, LDLC and TG showed significant difference between yellow wine polyphenolic compounds intervention groups and rosuvastain intervention group （P〈0.05）. No significant difference of plasma high density lipoprotein cholesterol （HDLC） level among groups were observed （P〉0.05）. Compared to high fat group, the atherosclerosis lesion area in rosuvastain intervention group and yellow wine polyphenolic compounds 10, 30, 50 mg/（kg·d） intervention groups decreased by 74.14%, 18.51%, 40.09%, 38.42% （P〈0.01）, respectively. Use of yellow wine polyphenolic compounds and rosuvastain significantly reduced the atherosclerosis lesion area （P〈0.01）. The yellow wine polyphenolic compounds and rosuvastain could down-regulate MMP-2, MMP-9 expression and activities （P〈0.01）, whereas expression of TIMP-1, TIMP-2 were up-regulated （P〈0.01）. Conclusions The yellow wine polyphenolic compounds is similar to the role of rosuvastain, which can improve dyslipidemia, reduce the expression and activities of MMP-2, MMP-9, at the same time promote the expression of TIMP-1, TIMP-2, improve the pathologic changes of atherosclerosis, indicating that they have benefic effects on cardiovascular system.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2013年第12期1069-1074,共6页
Chinese Journal of Arteriosclerosis
基金
卫生部科学研究基金-浙江省医药卫生重大科技计划项目(WKJ2011-2-018)
浙江省自然科学基金资助项目(Y2100535)
