Mackness M, Boullier A, Hennuyer N, Mackness B, Hall M, Tailleux A, Duriez P, Delfly B, Durrington P, Fruchart J C, Duverger N, Caillaud J M, Castro G
Department of Medicine, University of Manchester, Manchester, United Kingdom.
Biochem Biophys Res Commun. 2000 Mar 5;269(1):232-6. doi: 10.1006/bbrc.2000.2265.
Serum paraoxonase (PON1) is believed to protect against the development of atherosclerosis because of its ability to retard the oxidation of low-density lipoprotein (LDL) by hydrolysing LDL-associated phospholipid and cholesteryl-ester hydroperoxides. We have examined the relationship between PON1 and atherosclerosis development in transgenic rabbits overexpressing human apolipoprotein (apo) A-I and nontransgenic littermates fed a pro-atherogenic diet. PON1 activity was higher in transgenic (4006.1 +/- 716.7 nmol/min/ml) compared to control (3078.5 +/- 623.3 nmol/min/ml) rabbits (P < 0.01) while high-density lipoprotein (HDL) cholesterol was 1.84 +/- 0.54 mmol/L in transgenic rabbits and 0.57 +/- 0.21 mmol/L in control rabbits (P = 0.0001). After feeding rabbits a high-cholesterol diet for 14 weeks HDL-cholesterol fell by 70% in both transgenic and control rabbits (P < 0.001 compared to week 0) PON1 activity fell by 50% in both groups of rabbits (P < 0. 01 compared to week 0). The amount of thoracic aortic surface area covered by lesions was 29 +/- 16% in the control group and 26 +/- 15% in the transgenic group (P = NS). A pro-atherosclerotic diet reduces PON1 which may exaggerate the effects of the diet on the development of atherosclerosis.
血清对氧磷酶（PON1）被认为可预防动脉粥样硬化的发展，因为它能够通过水解与低密度脂蛋白（LDL）相关的磷脂和胆固醇酯氢过氧化物来延缓LDL的氧化。我们研究了过表达人载脂蛋白（apo）A-I的转基因兔和喂食促动脉粥样硬化饮食的非转基因同窝仔兔中PON1与动脉粥样硬化发展之间的关系。与对照兔（3078.5±623.3 nmol/min/ml）相比，转基因兔（4006.1±716.7 nmol/min/ml）的PON1活性更高（P<0.01），而转基因兔的高密度脂蛋白（HDL）胆固醇为1.84±0.54 mmol/L，对照兔为0.57±0.21 mmol/L（P = 0.0001）。给兔子喂食高胆固醇饮食14周后，转基因兔和对照兔的HDL胆固醇均下降了70%（与第0周相比，P<0.001），两组兔子的PON1活性均下降了50%（与第0周相比，P<0.01）。对照组胸主动脉病变覆盖的表面积为29±16%，转基因组为26±15%（P =无显著性差异）。促动脉粥样硬化饮食会降低PON1，这可能会夸大饮食对动脉粥样硬化发展的影响。
