Monroe P, Vlahcevic Z R, Swell L
Gastroenterology. 1983 Oct;85(4):820-9.
Fifteen patients with liver disease were found to have marked reductions in both plasma lecithin-cholesterol acyltransferase activity (62%) and cholesterol ester concentration (46%) when compared with 11 normal subjects. The changes in cholesterol ester concentration were confined to high-density lipoprotein and very-low-density lipoprotein; the low-density lipoprotein fraction was not significantly altered. Examination of the plasma lecithin and lipoprotein cholesterol esters revealed that patients with liver disease had significantly greater amounts of saturated and monounsaturated fatty acids and less linoleic acid than normal subjects. Lipoprotein cholesterol ester kinetic studies were carried out in 2 normal subjects and 2 severely cirrhotic patients who simultaneously received [14C]mevalonic acid and high-density lipoprotein labeled with free [3H]cholesterol. A lipoprotein cholesterol ester model was developed that fit both the 3H and 14C data. The precursors of high-density lipoprotein cholesterol esters were free cholesterol and low-density lipoprotein cholesterol esters; the distribution pattern was in favor of low-density lipoprotein cholesterol esters in both groups of subjects (71% for normals and 88% for cirrhotics). The turnover of high-density lipoprotein cholesterol esters was similar in both groups of subjects, but the flux of free cholesterol into high-density lipoprotein cholesterol esters was greatly reduced in the cirrhotic patients. In cirrhotic patients, this represented only 9% and 12% of the total lipoprotein cholesterol ester synthesized; in the normal subjects, the values were 68% and 74%. The turnover of very-low-density lipoprotein cholesterol esters was greatly suppressed in the cirrhotic patients, and their precursor sources were high-density lipoprotein cholesterol esters and tissue free cholesterol. The low-density lipoprotein cholesterol ester precursors were very-low-density lipoprotein, low-density lipoprotein, and tissue free cholesterol. In the cirrhotic patients, much greater proportions (78% and 88%) of low-density lipoprotein cholesterol ester were derived from free cholesterol. Also, the turnover rates of these esters were reduced in the cirrhotic patients. The present report has provided evidence that cirrhotic patients derive most of their plasma lipoprotein cholesterol esters from an acyl-CoA-cholesterol acyltransferase free-cholesterol tissue source--most likely the intestine. By contrast, in normal subjects, the major contribution to plasma esters is via the introduction of newly formed cholesterol esters into the high-density lipoprotein fraction.
与11名正常受试者相比，15名肝病患者的血浆卵磷脂胆固醇酰基转移酶活性（降低62%）和胆固醇酯浓度（降低46%）均显著降低。胆固醇酯浓度的变化仅限于高密度脂蛋白和极低密度脂蛋白；低密度脂蛋白部分无显著改变。对血浆卵磷脂和脂蛋白胆固醇酯的检测显示，肝病患者的饱和脂肪酸和单不饱和脂肪酸含量明显高于正常受试者，而亚油酸含量则低于正常受试者。对2名正常受试者和2名重度肝硬化患者进行了脂蛋白胆固醇酯动力学研究，这2名患者同时接受了[14C]甲羟戊酸和游离[3H]胆固醇标记的高密度脂蛋白。建立了一个脂蛋白胆固醇酯模型，该模型与3H和14C数据均相符。高密度脂蛋白胆固醇酯的前体是游离胆固醇和低密度脂蛋白胆固醇酯；在两组受试者中，分布模式均有利于低密度脂蛋白胆固醇酯（正常人为71%，肝硬化患者为88%）。两组受试者中高密度脂蛋白胆固醇酯的周转率相似，但肝硬化患者中游离胆固醇进入高密度脂蛋白胆固醇酯的通量大大降低。在肝硬化患者中，这仅占合成的总脂蛋白胆固醇酯的9%和12%；在正常受试者中，该值为68%和74%。肝硬化患者中极低密度脂蛋白胆固醇酯的周转率受到极大抑制，其前体来源是高密度脂蛋白胆固醇酯和组织游离胆固醇。低密度脂蛋白胆固醇酯的前体是极低密度脂蛋白、低密度脂蛋白和组织游离胆固醇。在肝硬化患者中，更大比例（78%和88%）的低密度脂蛋白胆固醇酯来自游离胆固醇。此外，这些酯的周转率在肝硬化患者中也降低了。本报告提供的证据表明，肝硬化患者血浆脂蛋白胆固醇酯的大部分来自酰基辅酶A胆固醇酰基转移酶非依赖性胆固醇组织来源——最有可能是肠道。相比之下，在正常受试者中，血浆酯的主要来源是将新形成的胆固醇酯引入高密度脂蛋白部分。
