Armstrong M L, Mathur S N, Sando G N, Megan M B
Am J Pathol. 1986 Nov;125(2):339-48.
The authors studied xanthomatous skin in cholesterol-fed rabbits for changes in lipid content and in activities of enzymes regulating intracellular lipid content. After 80 days of hypercholesterolemic diet, xanthomas were widespread and changes in lipid metabolism were marked. In both tissue homogenates and cell membrane pellets, unesterified cholesterol and phospholipids increased 2-fold to 6-fold, and cholesteryl esters increased about 30-fold. Tissue triglycerides, however, decreased to half the levels found in control skin. Cholesterol esterification rates, measured by activity of acyl coenzyme A: cholesterol acyltransferase, increased moderately to markedly; hydrolase activity against 4-methylumbelliferyl oleate also increased at both acid and neutral pH, but hydrolase activity against cholesterol oleate increased only at acid pH. Thus, hypercholesterolemia caused striking increases in intracellular cholesterol esterification rates, increases in lipase activity at both neutral and acid pH, and increases in cholesteryl ester hydrolase activity at acid pH. Increases in cholesterol-esterifying activity uniformly exceeded increases in cholesteryl ester hydrolytic activity in congruence with net accumulation of cholesteryl ester. Skin xanthoma grade, however, had no consistent relation to the cholesterol esterification rates. Instead, the enzyme data suggested that marked abnormalities of lipid metabolism are diffusely distributed through dermal tissue as a precondition for the focal emergence of xanthomas.
作者研究了喂食胆固醇的兔子的黄色瘤皮肤，以观察脂质含量以及调节细胞内脂质含量的酶活性的变化。在高胆固醇饮食80天后，黄色瘤广泛出现，脂质代谢变化显著。在组织匀浆和细胞膜沉淀中，未酯化胆固醇和磷脂增加了2至6倍，胆固醇酯增加了约30倍。然而，组织甘油三酯降至对照皮肤中发现水平的一半。通过酰基辅酶A：胆固醇酰基转移酶活性测定的胆固醇酯化率适度至显著增加；在酸性和中性pH下，针对4-甲基伞形酮油酸酯的水解酶活性也增加，但针对胆固醇油酸酯的水解酶活性仅在酸性pH下增加。因此，高胆固醇血症导致细胞内胆固醇酯化率显著增加，中性和酸性pH下脂肪酶活性增加，酸性pH下胆固醇酯水解酶活性增加。胆固醇酯化活性的增加始终超过胆固醇酯水解活性的增加，这与胆固醇酯的净积累一致。然而，皮肤黄色瘤分级与胆固醇酯化率没有一致的关系。相反，酶数据表明脂质代谢的显著异常在真皮组织中广泛分布，这是黄色瘤局部出现的前提条件。
