Antiatherogenic effects of a novel lipoprotein lipase-enhancing agent in cholesterol-fed New Zealand white rabbits
Antiatherogenic effects of a novel lipoprotein lipase-enhancing agent in cholesterol-fed New Zealand white rabbits
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DOI：
10.1161/01.atv.17.11.2601
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发表时间：
1997-11-01
影响因子：
8.7
通讯作者：
Tomita, T
中科院分区：
文献类型：
--
作者：
Chiba, T;Miura, S;Tomita, T
根据我们的报告，给大鼠服用4-二氧氧磷酰甲基- n -（4-溴-2-氰苯基）苯酰胺（NO-1886）可以通过增加酶质量来提高肝磷脂后脂蛋白脂肪酶（LPL）的活性，我们现在研究NO-1886在胆固醇喂养的新西兰大白兔中的抗动脉粥样硬化作用。试验20周，4组雄性家兔分别饲喂普通兔粮（正常对照组）、含胆固醇0.25%的家兔粮（对照组）和添加0.5%和1.0% NO-1886的胆固醇家兔粮。第10周，与对照组相比，0.5% NO-1886组的肝蛋白后LPL活性提高了30%，1.0% NO-1886组提高了40%。血浆胆固醇水平曲线下面积在三个胆固醇喂养组中没有差异，而高密度脂蛋白胆固醇曲线下面积在两个NO-1886组中比对照组大约大两倍，血浆甘油三酯曲线下面积降低到正常对照组的水平。LPL活性与高密度脂蛋白胆固醇（r= 0.764, n=18）和甘油三酯（r=- 0.627, n=18）相关。摄入NO-1886后，相对动脉粥样硬化面积、主动脉胆固醇和甘油三酯含量分别降至对照组的25%、60%和55%左右。LPL、HDL胆固醇和甘油三酯的多元回归分析表明，HDL胆固醇对主动脉胆固醇积累的保护作用最强，甘油三酯对动脉粥样硬化区有保护作用。我们得出结论，NO-1886通过增加LPL活性，从而增加高密度脂蛋白胆固醇和降低甘油三酯，而不显著影响血浆胆固醇水平，从而阻止动脉粥样硬化的发展。
Following our report that administration of 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl) benzamide (NO-1886) to rats elevated postheparin lipoprotein lipase (LPL) activity through an increase in the enzyme mass, we now investigate antiatherogenic effects of NO-1886 in cholesterol-fed New Zealand White rabbits. For 20 weeks, four groups of male rabbits received regular rabbit chow (the normal control), 0.25% cholesterol-containing chow (the control), and cholesterol chow supplemented with 0.5% and 1.0% NO-1886, respectively. Postheparin LPL activity at week 10 was raised by 30% in 0.5% of the NO-1886 group and 40% in 1.0% of the NO-1886 group compared with those in the control. The area under the curve of plasma cholesterol level was not different in three cholesterol-fed groups whereas the area under the curve of HDL cholesterol was approximately twofold greater in the two NO-1886 groups than in the control, and the area under the curve of plasma triglyceride was reduced to the level of the normal control. LPL activity was correlated with HDL cholesterol (r=.764, n=18) and triglyceride (r=-.627, n=18). Relative atheromatous area, aortic cholesterol, and triglyceride contents were reduced to approximately 25%, 60%, and 55%, respectively, of the control values by NO-1886 ingestion. Multiple regression analysis of LPL, HDL cholesterol, and triglyceride indicated that HDL cholesterol was the most powerful protector against aortic cholesterol accumulation, and triglyceride was the one to protect against the atheromatous area. We concluded that NO-1886 prevented the development of atherosclerosis through increasing LPL activity with a consequent increase in HDL cholesterol and a decrease in triglyceride without a significant influence of plasma cholesterol level.