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

在敲除雌性激素合成酶，芳香化酶（AR）基因的小鼠（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，雌雄小鼠均可见脂肪肝。因此，该小鼠有望成为研究雌激素缺乏导致的动脉粥样硬化的良好动物模型。研究表明，在高胆固醇饮食的ARKO小鼠和正常小鼠中均未观察到动脉粥样硬化病变。由于小鼠是大鼠型动物，其血清中高密度脂蛋白含量很高，因此在小鼠中未观察到动脉粥样硬化病变，而不像致动脉粥样硬化动物、人或兔，其血清中高密度脂蛋白含量很低。因此，缺乏雌性激素、雌激素的ARKO小鼠可能很难观察到动脉粥样硬化病变。研究表明，产生高密度脂蛋白载脂蛋白组分的载脂蛋白E基因缺乏的小鼠是一种很好的模型动物，以动脉粥样硬化为特征的动脉粥样硬化更多，因为即使在正常饮食的小鼠中也会自发观察到动脉粥样硬化。在本研究中，我们试图用AR和Apo E缺陷小鼠（DBKO小鼠）建立新的动物模型，以观察雌激素缺乏是否作为动脉粥样硬化发病的积极因素。DBKO小鼠血清总胆固醇含量为：♂，1368±638mg/dl (n=8)；♀，704±245mg/dl （n=7）。血清中甘油三酯含量为：♂，969±869mg/dl (n=8)；♀，251±121mg/dl （n=7）。这些结果表明DBKO小鼠明显比载脂蛋白E低的小鼠高脂血症更严重。我们尝试观察DBKO小鼠的动脉病变情况。在Apo E KO小鼠中，雄性和雌性小鼠的动脉粥样硬化病变面积百分比分别为38±7% （n=9）、39±7% (n=11)，而DBKO小鼠的动脉粥样硬化病变面积百分比分别为28±6% （n=12）、16±8% （n=8）。这些观察结果表明，载脂蛋白E - KO小鼠芳香化酶基因缺失导致动脉壁动脉粥样硬化的减少。原因目前还不清楚，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。这种差异应在不久的将来得到澄清。少

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