Dell R B, Mott G E, Jackson E M, Ramakrishnan R, Carey K D, McGill H C, Goodman D S
J Lipid Res. 1985 Mar;26(3):327-37.
Cholesterol turnover was studied in four baboons by injecting [14C]cholesterol 186 days and [3H]cholesterol 4 days before necropsy, and fitting a two- or three-pool model to the resulting specific activity-time data. At necropsy, cholesterol mass and specific activity were determined for the total body (minus the central nervous system) and for many tissues. A pool model permits the estimation, from the plasma specific activity-time curve alone, of total body cholesterol within a limited range, depending upon the extent of side pool synthesis. The principal aim of this study was to estimate the extent of cholesterol synthesis in the side pools of the model, by computing the amount of side pool synthesis needed to equal the measured total body cholesterol. Central pool synthesis varied from 61 to 89% of the total cholesterol production rate. Thus, approximately 25% (11 to 39%) of the production rate arose from peripheral (pool 3 for the three-pool, and pool 2 for the two-pool model) cholesterol synthesis. Moreover, the finding that the measured total body cholesterol fell within the range obtained from the kinetic analysis by using reasonable assumptions (namely, that zero or that half the production rate occurred in the side pools), provides evidence for the physiological validity of the model. A second aim of this study was to explore cholesterol turnover in various tissues. A pool model predicts that rapidly turning over tissues will have higher specific activities at early times and lower specific activities at later times after injection of tracer relative to slowly turning over tissues, except where significant synthesis occurs. Tissues were ranked 1 to 17 for 3H and 17 to 1 for 14C cholesterol specific activity values. Except for the GI tract and testis, the tissues had similar ranks for both 3H and 14C, further validating model predictions. Results in all four baboons were similar. Turnover rates for the different tissues loosely fell into three groups which were turning over at fast, intermediate, and slow rates. Finally, the magnitude of variation of cholesterol specific activity was moderate for several distributed tissues (fat, muscle, arteries, and the alimentary tract), but was small for liver. Cholesterol turnover in serial biopsies of skin, muscle, and fat could, however, be fitted with a single pool to estimate tissue turnover rates.
通过在尸检前186天注射[14C]胆固醇和4天前注射[3H]胆固醇，并对所得的比活度-时间数据拟合二池或三池模型，对4只狒狒的胆固醇周转率进行了研究。在尸检时，测定了全身（不包括中枢神经系统）和许多组织的胆固醇质量和比活度。池模型允许仅根据血浆比活度-时间曲线，在有限范围内估计全身胆固醇，这取决于侧池合成的程度。本研究的主要目的是通过计算使测得的全身胆固醇相等所需的侧池合成量，来估计模型侧池中胆固醇合成的程度。中央池合成占总胆固醇产生率的61%至89%。因此，大约25%（11%至39%）的产生率来自外周（三池模型中的池3和二池模型中的池2）胆固醇合成。此外，测得的全身胆固醇落在通过合理假设（即侧池中零或一半的产生率）从动力学分析获得的范围内，这一发现为该模型的生理有效性提供了证据。本研究的第二个目的是探索各种组织中的胆固醇周转率。池模型预测，相对于周转缓慢的组织，周转迅速的组织在注射示踪剂后的早期将具有较高的比活度，而在后期具有较低的比活度，但在发生大量合成的情况下除外。根据3H和14C胆固醇比活度值，将组织从1到17进行排序。除胃肠道和睾丸外，3H和14C的组织排序相似，进一步验证了模型预测。所有4只狒狒的结果相似。不同组织的周转率大致分为三组，分别以快、中、慢速率周转。最后，几种分布组织（脂肪、肌肉、动脉和消化道）的胆固醇比活度变化幅度适中，但肝脏的变化幅度较小。然而，皮肤、肌肉和脂肪的连续活检中的胆固醇周转率可以用单一池拟合，以估计组织周转率。
