Myers S I, Russell D H, Parks L, Reed M K
Department of Surgery, University of Texas Southwestern Medical Center, Dallas.
Prostaglandins Leukot Essent Fatty Acids. 1991 Sep;44(1):31-6. doi: 10.1016/0952-3278(91)90141-q.
Atherosclerosis was induced in male rabbits by administration of a 2% cholesterol diet for up to 18 weeks. The animals were assessed for aortic microsomal prostanoid synthesis, morphologic assessment and serum cholesterol levels. Serum levels of cholesterol increased from control values of 84 +/- 9 ng/dl to 1632 +/- 227 ng/dl at 2 weeks (20-fold increase), and 4859 +/- 829 ng/dl at 9 weeks (57-fold increase). Aortic microsomal prostacyclin synthesis fell significantly at 2 weeks of cholesterol feeding which predated the morphologic appearance of atherosclerotic plaque in the 7 week group. Aortic microsomal PGI2 synthesis significantly increased by 7 weeks and did not fall until the 18 week group when a highly significant increase in aortic plaque developed. These findings suggest a triphasic response of aortic PGI2 synthesis with the development of early atherosclerosis. Phase one is a fall in aortic PGI2 synthesis which predates the appearance of plaque. In phase 2, a significant rise in aortic PGI2 with the appearance of plaque could represent compensation of aortic endothelium to prevent further plaque development. In phase 3, decreased aortic PGI2 could indicate replacement of normal endothelium by atherosclerotic plaque.
通过给予雄性兔子2%胆固醇饮食长达18周来诱导动脉粥样硬化。对这些动物进行主动脉微粒体前列腺素合成、形态学评估和血清胆固醇水平的测定。血清胆固醇水平从对照组的84±9 ng/dl在2周时增加到1632±227 ng/dl（增加20倍），在9周时增加到4859±829 ng/dl（增加57倍）。在喂食胆固醇2周时，主动脉微粒体前列环素合成显著下降，这早于7周组动脉粥样硬化斑块的形态学出现。主动脉微粒体PGI2合成在7周时显著增加，直到18周组出现高度显著的主动脉斑块增加时才下降。这些发现提示主动脉PGI2合成在早期动脉粥样硬化发展过程中呈三相反应。第一阶段是主动脉PGI2合成下降，早于斑块出现。在第二阶段，随着斑块出现主动脉PGI2显著升高可能代表主动脉内皮的代偿，以防止斑块进一步发展。在第三阶段，主动脉PGI2下降可能表明正常内皮被动脉粥样硬化斑块取代。
