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

在雌性激素合成酶(AR)基因被敲除的小鼠(ARKO小鼠)中，无法在血清中检测到雌激素。雌鼠卵巢发育异常，雌雄小鼠均可见脂肪肝。因此，小鼠有望成为研究雌激素缺乏所致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，没有观察到动脉粥样硬化病变。由于小鼠是一种大鼠类型的动物，其中血清中的高密度脂蛋白含量非常高，所以不像致动脉粥样硬化的动物、人或兔那样，在小鼠中观察到动脉粥样硬化病变，而不是在血清中高密度脂蛋白含量非常低的动物中。因此，在雌性激素雌激素缺乏的ARKO小鼠中很难观察到动脉粥样硬化病变。已有研究表明，产生高密度脂蛋白成分的载脂蛋白E基因缺陷的小鼠是研究STU…的良好模型动物更多的是以动脉粥样硬化为特征的动脉粥样硬化，因为即使在正常饮食的小鼠中也能自发地观察到动脉粥样硬化。在本研究中，我们试图利用AR和载脂蛋白E缺陷小鼠(DBKO小鼠)建立一种新的动物模型，以了解雌激素缺乏是否在动脉粥样硬化的发病机制中起积极作用。小鼠血清总胆固醇含量：♂为1368±638 mg/dl(n=8)，♀为704±245 mg/dl(n=7)。血清甘油三酯含量：♂为96 9±86 9 mg/dl(n=8)，♀为2 5 1±121 mg/dl(n=7)。这些结果表明，DBKO小鼠的高脂血症明显高于apo E缺乏的小鼠。观察DBKO小鼠动脉病变情况。ApoE-KO组雌雄小鼠动脉粥样硬化斑块面积百分比分别为38±7%(n=9)和39±7%(n=11)，而DBKO组雌雄小鼠分别为28±6%(n=12)和16±8%(n=8)。提示apo E KO小鼠芳香酶基因缺失可导致动脉壁动脉粥样硬化程度减轻。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。这种差异应该在不久的将来得到澄清。较少

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