The effect of alloxan diabetes on experimental cholesterol atherosclerosis in the rabbit.
The effect of alloxan diabetes on experimental cholesterol atherosclerosis in the rabbit.
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DOI：
10.1084/jem.89.6.611
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发表时间：
1949-06-01
影响因子：
15.3
通讯作者：
McMILLAN, G C
中科院分区：
文献类型：
--
作者：
DUFF, G L;McMILLAN, G C
本文比较了正常家兔和四氧嘧啶致持续性糖尿病家兔的胆固醇喂养效果。在两组动物中，通过喂食程序诱导了程度相当的高胆固醇血症。然而，在糖尿病兔中产生的主动脉粥样硬化的严重程度远低于非糖尿病对照动物。事实上，很大一部分糖尿病动物没有出现动脉粥样硬化。对糖尿病家兔肝、脾、肾上腺中脂质存款也有类似的抑制作用。与四氧嘧啶糖尿病相关的实验性胆固醇动脉粥样硬化的发展的抑制与四氧嘧啶本身的给药无关。它不依赖于动物的性别或体重，也不依赖于胆固醇的每日剂量，给药形式，也不依赖于胆固醇喂养的持续时间。它也与我们实验过程中发生的体重变化和胆固醇给药诱导的高胆固醇血症的实际程度无关。此外，在主动脉或观察到抑制作用的其他器官中，均无形态学基础的大体或组织学证据。仅观察到两个因素始终与胆固醇饲喂的预期形态学效应抑制相关，即糖尿病状态和明显高于对照动物的可见脂血症程度。在这些实验中观察到的抑制作用似乎取决于糖尿病状态中隐含的或与之密切相关的一些尚未确定的因素。所提供的实验数据清楚地表明，高胆固醇血症不是实验性胆固醇动脉粥样硬化发生的唯一因素，但另一个因素，在我们的实验中呈现的放射性物质对动脉损伤的产生必不可少。鉴于在四氧嘧啶糖尿病兔中观察到的对实验性胆固醇动脉粥样硬化发展的抑制作用，在另一系列实验中研究了四氧嘧啶糖尿病对这种动脉病变消退的影响。在停止胆固醇喂养后最长持续4个月的时间内，未证明对退化的影响。我们的两个系列实验的结果，一起考虑，表明在动脉壁中的脂质沉积的过程是由不同的因素，这些因素是在脂质沉积后的去除过程中起作用的。在四氧嘧啶糖尿病家兔中，对实验性胆固醇动脉粥样硬化发展的抑制必须依赖于对脂质沉积过程的干扰，而不是依赖于脂质沉积时迅速清除脂质的过程。我们的实验结果没有发现直接应用于人类糖尿病的动脉疾病问题。尽管如此，我们所采用的实验程序为进一步设计实验提供了新的基础，这些实验旨在阐明支配动脉壁脂质沉积过程的未知因素的性质。
A comparison was made of the effects of cholesterol feeding in normal rabbits and in rabbits rendered persistently diabetic by means of alloxan. In the two groups of animals hypercholesterolemia of comparable degree was induced by the feeding procedure. Nevertheless, the severity of the atherosclerosis of the aorta produced in the diabetic rabbits was much less than in the non-diabetic control animals. Indeed, a large proportion of the diabetic animals presented no atherosclerosis whatever. There was a similar inhibition of the deposit of lipid substances in the liver, spleen, and adrenal glands of the diabetic rabbits. The inhibition of the development of experimental cholesterol atherosclerosis which was associated with the presence of alloxan diabetes was independent of the administration of alloxan per se. It was not dependent on the sex or weight of the animal, nor upon the daily dosage of cholesterol, the form in which it was administered, nor the duration of cholesterol feeding. It was also independent of changes in body weight occurring during the course of our experiments and of the actual degree of hypercholesterolemia induced by the administration of cholesterol. In addition, there was no gross or histological evidence of a morphological basis for the inhibitory effect either in the aorta or in the other organs in which it was observed. Only two factors were observed to be consistently associated with the inhibition of the expected morphological effects of cholesterol feeding, namely, the diabetic state and a degree of visible lipemia considerably greater than that observed in the control animals. The inhibitory effect observed in these experiments would appear to depend upon some as yet undetermined factor or factors implicit in the diabetic state or closely associated with it. The experimental data presented demonstrate clearly that hypercholesterolemia is not the sole factor concerned in the genesis of experimental cholesterol atherosclerosis, but that another factor, or factors, rendered inoperative in our experiments must be essential to the production of the arterial lesions. In view of the inhibitory effect on the development of experimental cholesterol atherosclerosis observed in alloxan-diabetic rabbits, the effect of alloxan diabetes on the retrogression of such arterial lesions was studied in another series of experiments. No effect on retrogression could be demonstrated within periods lasting up to a maximum of 4 months after the cessation of cholesterol feeding. The results of our two series of experiments, considered together, indicate that the process of deposition of lipids in the arterial walls is governed by factors different from those that are operative in the process of removal of lipids after they have been deposited. The inhibition of the development of experimental cholesterol atherosclerosis in alloxan-diabetic rabbits must depend on interference with the process of deposition of lipids and not on a process of removal of lipids as fast as they are deposited. Our experimental results find no direct application to the problem of arterial disease in human diabetes. Nevertheless, the experimental procedures that we have employed provide a new basis for the design of further experiments directed toward the elucidation of the nature of the unknown factors that govern the process of lipid deposition in the walls of arteries.