Fuller G C, Matoney A L, Fisher D O, Fausto N, Cardinale G J
Atherosclerosis. 1976 Sep;24(3):483-90. doi: 10.1016/0021-9150(76)90140-4.
Increased aortic and liver prolyl hydroxylase activity has been suggested as an early biochemical indicator of the fibrotic changes which occur in rabbits with injury induced arteriosclerosis. Daily administration of epinephrine (0.025-0.050 mg/kg, i.v.) and thyroxine (0.050 mg/kg, i.p.) to rabbits for 3 weeks produced aortic fibrous plaques with a 4-fold increase in aortic prolyl hydroxylase and also a 5-fold increase in liver prolyl hydroxylase. Histopathologically, the livers of these rabbits show subcapsular areas of necrosis. When total prolyl hydroxylase related antigen was measured. the increase in liver prolyl hydroxylase activity accounted for only a small portion of the total prolyl hydroxylase antigen. However, in the aorta a majority of the increase in antigen is due to the increased amount of enzyme. DNA content per aorta was unchanged and RNA content increased in the aortic tissue of the arteriosclerotic rabbits. However DNA and RNA levels increased 60% in the livers of arteriosclerotic rabbits. In vitro incorporation of radioactively labeled proline into collagenase digestable protein was at least 2-fold greater in aorta and liver minces from arteriosclerotic rabbits. Michaelis--Menten kinetic parameters were obtained for the liver prolyl hydroxylase purified by affinity chromatography from arteriosclerotic rabbits. The Km for the enzyme from treated animals was not significantly different from control. However, the Vmax of the enzyme purified from diseased liver was 4-fold greater when compared to controls.
主动脉和肝脏脯氨酰羟化酶活性增加被认为是家兔损伤诱导性动脉硬化中发生的纤维化变化的早期生化指标。每天给家兔静脉注射肾上腺素（0.025 - 0.050毫克/千克）和腹腔注射甲状腺素（0.050毫克/千克），持续3周，会产生主动脉纤维斑块，主动脉脯氨酰羟化酶增加4倍，肝脏脯氨酰羟化酶也增加5倍。组织病理学检查显示，这些家兔的肝脏出现包膜下坏死区域。当测量总脯氨酰羟化酶相关抗原时，肝脏脯氨酰羟化酶活性的增加仅占总脯氨酰羟化酶抗原的一小部分。然而，在主动脉中，抗原增加的大部分是由于酶量的增加。每根主动脉的DNA含量未变，而动脉硬化家兔主动脉组织中的RNA含量增加。然而，动脉硬化家兔肝脏中的DNA和RNA水平增加了60%。来自动脉硬化家兔的主动脉和肝脏匀浆中，放射性标记脯氨酸体外掺入胶原酶可消化蛋白的量至少是正常家兔的2倍。通过亲和层析从动脉硬化家兔肝脏中纯化得到脯氨酰羟化酶，并获得了米氏动力学参数。处理动物的酶的Km与对照组无显著差异。然而，与对照组相比，从患病肝脏中纯化的酶的Vmax增加了4倍。
