FOOD FACTORS THAT PROTECT ATHEROSCLEROSIS-ATTEMPTS USING MICE DEFICIENT IN FEMALE HORMONE SYNTHASE AND APOLIPOPROTEIN E GENES

保护动脉粥样硬化的食物因素——使用缺乏女性激素合成酶和载脂蛋白 E 基因的小鼠进行的尝试

• 批准号: 16500528
• 负责人: HARA Takayuki
• 金额: $ 1.92万
• 依托单位: NAKAMURA GAKUEN UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500528/
• 关键词: FEMALE HORMONE; ESTROGEN; ATHEROSCLEROSIS; KOCKOUT MOUSE; AROMATASE; FOOD FACTORS; PROTECTION; CHOLESTEROL

In mice whose gene for female hormone synthase, aromatase (AR) was knocked out (ARKO mice), estrogen cannot be detected in the serum. The abnormal development of ovary is observed in the female mice, and the fat liver is observed in both sex mice. Thus, the mice are expected to be a good animal model for the study of atherosclerosis which depends on estrogen deficiency. It has been shown that atherosclerotic lesions were not observed in ARKO mice which were kept on the high cholesterol diet, as well as normal mice. Since mouse is a rat type animal, in which HDL content is very high in the serum, atherosclerotic lesions are not observed in the mouse not like an atherogenic animal, human or rabbit in which HDL content is very low in the serum. Therefore, atherosclerotic lesions may be hardly observed in ARKO mice deficient in female hormone, estrogen.It has been shown that mice deficient in apo E gene which produces a component of apolipoproteins of HDL is a good model animal for the stu … More dy of atherosclerosis characterized by atheroma, because the atherosclerosis was spontaneously observed in the mice even with a normal diet. In this study, we tried to make a new animal model using AR and Apo E deficient mice (DBKO mice) to see whether or not estrogen deficiency acts as a positive factor of pathogenesis of atherosclerosis. Total cholesterol contents in the serum of DBKO mice were as follows : ♂, 1368±638mg/dl (n=8) ; ♀, 704±245mg/dl (n=7). The triglyceride contents in the serum were as follows : ♂, 969±869mg/dl (n=8) : ♀, 251±121mg/dl (n=7). These results indicate that DBKO mice are clearly more hyperlipidemic than apo E decicient mice. We tried to observe the lesions of artery of DBKO mice. In Apo E KO mice, atherosclerotic lesions expressed as % of area were 38±7% (n=9), 39±7% (n=11) in male and female mice, respectively, whereas those in DBKO mice were 28±6% (n=12), 16±8% (n=8) in male and female mice, respectively. These observations suggest that aromatase gene deficiency of apo E KO mice results on the decrease of atherosclerosis of the arterial wall. The reasons are not understood well at this point, but in this animal model, cholesterol itself may not be a sole factor of atherosclerosis. The discrepancy should be clarified in the near future. Less

在雌性激素合成酶芳香化酶（AR）基因被敲除的小鼠（ARKO小鼠）中，血清中无法检测到雌激素。雌性小鼠卵巢发育异常，雌雄小鼠均出现脂肪肝。因此，小鼠有望成为研究依赖雌激素缺乏的动脉粥样硬化的良好动物模型。已经表明，在保持高胆固醇饮食的ARKO小鼠以及正常小鼠中未观察到动脉粥样硬化病变。由于小鼠是血清中HDL含量非常高的大鼠型动物，因此在小鼠中未观察到动脉粥样硬化病变，这与血清中HDL含量非常低的致动脉粥样硬化动物、人或兔不同。因此，在雌性激素-雌激素缺乏的ARKO小鼠中几乎观察不到动脉粥样硬化病变，已经表明，产生HDL载脂蛋白组分的载脂蛋白E基因缺乏的小鼠是研究动脉粥样硬化病变的良好模型动物。 ...更多信息 因为即使在正常饮食的小鼠中也自发地观察到动脉粥样硬化。本研究利用AR和ApoE基因缺陷小鼠（DBKO小鼠）建立一种新的动物模型，探讨雌激素缺乏是否是动脉粥样硬化发病的一个积极因素。DBKO小鼠血清总胆固醇含量分别为1368± 638 mg/dl（n=8）和704± 245 mg/dl（n=7）。血清甘油三酯含量分别为：甘油三酯969± 869 mg/dl（n=8），甘油三酯251± 121 mg/dl（n=7）。这些结果表明，DBKO小鼠明显比apo E缺陷小鼠更高血压。观察DBKO小鼠动脉病变情况。在Apo E KO小鼠中，雄性和雌性小鼠的动脉粥样硬化病变（以面积%表示）分别为38±7%（n=9）和39±7%（n=11），而在DBKO小鼠中，雄性和雌性小鼠的动脉粥样硬化病变（以面积%表示）分别为28±6%（n=12）和16±8%（n=8）。这些观察结果表明，芳香化酶基因缺陷的载脂蛋白E基因敲除小鼠的结果减少动脉壁的动脉粥样硬化。原因尚不清楚，但在这个动物模型中，胆固醇本身可能不是动脉粥样硬化的唯一因素。这一差异应在不久的将来得到澄清。少