槲皮素和乙醇可抑制载脂蛋白 E 基因敲除小鼠动脉粥样硬化斑块的进展，同时上调对氧磷酶 1（PON1）基因表达和 PON1 活性。
Quercetin and ethanol attenuate the progression of atherosclerotic plaques with concomitant up regulation of paraoxonase1 (PON1) gene expression and PON1 activity in LDLR-/- mice.
机构信息
The Lipid Research Laboratory, Veterans Affairs Medical Center, Washington, District of Columbia 20422, USA.
出版信息
Alcohol Clin Exp Res. 2010 Sep 1;34(9):1535-42. doi: 10.1111/j.1530-0277.2010.01238.x. Epub 2010 Jun 25.
BACKGROUND
As moderate wine drinking is atheroprotective, it is clinically relevant to elucidate its possible mechanism/s of action/s. Our objective is to demonstrate the potential benefits of the wine components, quercetin and ethanol, on the development of aortic plaques with parallel changes in antiatherogenic factors.
METHODS AND RESULTS
The effects of quercetin and ethanol on the development of aortic atherosclerotic lesions, liver PON1 gene expression, and serum PON1 activity were measured in LDLR(-/-) mice on an atherogenic diet for 4 and 8 weeks. Depending on the duration and dosage of these modulators, 12.5 to 25 mg/dl quercetin (12.5Q to 25Q) and 18 to 25% ethanol, the magnitude of decreases in aortic lesions caused by moderate ethanol and quercetin ranged from 20 to 70% (p < 0.05 to p < 0.001) based on ultrasound biomicroscopy (UBM) analyses, and from 18 to 61% (p < 0.05 to p < 0.001) based on morphometric analyses. The composite plot of all the UBM and morphometric data showed significant correlation between these 2 methods (p = 0.0001, Pearson r = 0.79 for 4-week treatment; p = 0.000004, Pearson r = 0.84 for 8-week treatment). Concomitantly, 4-week treatments with 12.5Q and 18% ethanol up regulated liver PON1 mRNA by 41% (p < 0.05) and 37% (p < 0.05), respectively, accompanied by 92% (p < 0.001) and 61% (p < 0.001) increases in serum PON1 activity, respectively. The corresponding values after 8-week treatment with 12.5Q and 18% ethanol were 23% (p < 0.05) and 40% (p < 0.02) with respect to the up regulation of liver PON1 mRNA expression, while the stimulations of serum PON1 activity were 75% (p < 0.001) and 90% (p < 0.001), respectively.
CONCLUSIONS
Based on these findings, we conclude that quercetin and moderate ethanol significantly inhibit the progression of atherosclerosis by up regulating the hepatic expression of the antiatherogenic gene, PON1, with concomitant increased serum PON1 activity.
背景
适量饮酒具有抗动脉粥样硬化作用，因此阐明其可能的作用机制具有重要的临床意义。我们的目的是证明葡萄酒成分槲皮素和乙醇在抗动脉粥样硬化因子平行变化的情况下对主动脉斑块形成的潜在益处。
方法和结果
在 LDLR(-/-)小鼠的动脉粥样硬化饮食中，4 周和 8 周时，我们测量了槲皮素和乙醇对主动脉粥样硬化病变、肝脏 PON1 基因表达和血清 PON1 活性的影响。根据这些调节剂的持续时间和剂量，12.5 至 25mg/dl 的槲皮素（12.5Q 至 25Q）和 18%至 25%的乙醇，中等乙醇和槲皮素引起的主动脉病变减少幅度范围为 20%至 70%（超声生物显微镜[UBM]分析，p<0.05 至 p<0.001）和 18%至 61%（形态计量学分析，p<0.05 至 p<0.001）。所有 UBM 和形态计量学数据的综合图显示，这两种方法之间存在显著相关性（4 周治疗时 p=0.0001，Pearson r=0.79；8 周治疗时 p=0.000004，Pearson r=0.84）。同时，4 周的 12.5Q 和 18%乙醇处理分别使肝脏 PON1mRNA 上调 41%（p<0.05）和 37%（p<0.05），同时使血清 PON1 活性分别增加 92%（p<0.001）和 61%（p<0.001）。12.5Q 和 18%乙醇处理 8 周后，肝脏 PON1mRNA 表达的上调分别为 23%（p<0.05）和 40%（p<0.02），而血清 PON1 活性的刺激分别为 75%（p<0.001）和 90%（p<0.001）。
结论
基于这些发现，我们得出结论，槲皮素和适量乙醇通过上调抗动脉粥样硬化基因 PON1 的肝表达，并伴有血清 PON1 活性的增加，显著抑制动脉粥样硬化的进展。
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