Robins S J, Fasulo J M, Collins M A, Patton G M
J Lipid Res. 1985 Oct;26(10):1230-40.
The turnover of plasma cholesterol and de novo cholesterol synthesis were measured simultaneously in the live rat, immediately after administration of [3H]water together with a large volume exchange transfusion of whole blood prelabeled with [14C]cholesterol. It was possible to separate the exchange of unesterified cholesterol from the uptake and secretion of lipoprotein cholesteryl ester, and also to assess the impact of plasma cholesterol exchange on the measurement of in vivo rates of cholesterolgenesis by individual tissues. Cholesterol was measured by an HPLC procedure that effectively separated cholesterol from other structurally similar sterols, and synthesis was determined by the incorporation of [3H]water into cholesterol. Plasma unesterified cholesterol turnover was multiphasic and exceedingly rapid (initial T1/2, 4.1 min) in contrast to the near linear and much slower turnover of plasma cholesteryl ester (initial T1/2, 59.4 min). Plasma unesterified cholesterol equilibrated with different tissues at different rates, with the liver and adrenal equilibrating most rapidly. Full equilibration of plasma unesterified cholesterol was not achieved with any tissue during the course of this study. For rapidly exchanging tissues like the liver, which was responsible for about 60% of plasma unesterified cholesterol exchange, unesterified cholesterol appeared to be kinetically compartmentalized into rapidly, and much less rapidly, exchangeable pools. After [3H]water administration, the content of newly synthesized cholesterol was greatest in the liver, adrenal, and intestine, and appreciably lower in all other tissues studied. Hepatectomy and intestinal resection resulted in a profound reduction of newly synthesized cholesterol in the plasma and adrenal, but no certain change in the already low amounts at other sites. Thus, while it is clear that appreciable amounts of newly synthesized cholesterol in the adrenal were derived from the plasma by exchange, it was not possible to make this assessment for other selected individual tissues. When, however, newly synthesized cholesterol was determined in the total mass of all extrahepatic and extraintestinal tissues together, exchange could be calculated to account for close to 50% of the new cholesterol recovered in the carcass (in studies of 60 min duration). After correcting for exchange, the liver accounted for 82% of all newly synthesized cholesterol, the intestine for about 10%, and the remaining tissues of the body for just 9%. These results are in marked contrast to recent findings of others and demonstrate that in the live rat cholesterol synthesis is principally confined to the liver.
在给大鼠注射[³H]水并同时进行大量用[¹⁴C]胆固醇预标记的全血交换输血后，立即在活体大鼠中同时测量血浆胆固醇周转和从头胆固醇合成。能够将游离胆固醇的交换与脂蛋白胆固醇酯的摄取和分泌区分开来，还能评估血浆胆固醇交换对各个组织体内胆固醇生成率测量的影响。胆固醇通过高效液相色谱法测量，该方法能有效将胆固醇与其他结构相似的固醇分离，合成通过[³H]水掺入胆固醇来确定。与血浆胆固醇酯接近线性且慢得多的周转（初始半衰期，59.4分钟）相比，血浆游离胆固醇周转是多相的且极其迅速（初始半衰期，4.1分钟）。血浆游离胆固醇与不同组织以不同速率达到平衡，肝脏和肾上腺平衡最快。在本研究过程中，没有任何组织能使血浆游离胆固醇完全平衡。对于像肝脏这样负责约60%血浆游离胆固醇交换的快速交换组织，游离胆固醇在动力学上似乎被分隔到快速和慢得多的可交换池中。注射[³H]水后，肝脏、肾上腺和肠道中新合成胆固醇的含量最高，而在所有其他研究组织中明显较低。肝切除和肠切除导致血浆和肾上腺中新合成胆固醇大幅减少，但其他部位原本就很低的量没有明显变化。因此，虽然很明显肾上腺中相当数量的新合成胆固醇是通过交换从血浆中获得的，但无法对其他选定的单个组织进行这种评估。然而，当一起在所有肝外和肠外组织的总质量中测定新合成胆固醇时，在60分钟时长的研究中，可以计算出交换占胴体中回收的新胆固醇的近50%。校正交换后，肝脏占所有新合成胆固醇的82%，肠道约占10%，身体其余组织仅占9%。这些结果与其他人最近的发现形成鲜明对比，表明在活体大鼠中胆固醇合成主要局限于肝脏。
