维持内源性抗氧化活性及抑制脂质过氧化作为维生素E、洛伐他汀和氨氯地平抗动脉粥样硬化作用的共同机制。

Preservation of endogenous antioxidant activity and inhibition of lipid peroxidation as common mechanisms of antiatherosclerotic effects of vitamin E, lovastatin and amlodipine.

作者信息

Chen L, Haught W H, Yang B, Saldeen T G, Parathasarathy S, Mehta J L

机构信息

Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.

出版信息

J Am Coll Cardiol. 1997 Aug;30(2):569-75. doi: 10.1016/s0735-1097(97)00158-7.

DOI:10.1016/s0735-1097(97)00158-7

PMID:9247534

Abstract

OBJECTIVES

We sought to document the common mechanisms of the antiatherogenic effects of the cholesterol-lowering hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin, the dihydropyridine Ca2+ blocker amlodipine and the antioxidant vitamin E.

BACKGROUND

Vitamin E, HMG-CoA reductase inhibitors and Ca2+ blockers each inhibit atherosclerosis in hypercholesterolemic animals.

METHODS

New Zealand White rabbits were fed regular chow (Group A), chow with 1% cholesterol (Group B), 1% cholesterol diet plus lovastatin (Group C), 1% cholesterol diet plus vitamin E (Group D) or 1% cholesterol diet plus amlodipine (Group E) for 12 weeks. The extent of aortic atherosclerosis was measured by planimetry of the sudanophilic area. Malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured as indexes of lipid peroxidation and antioxidant activity, respectively.

RESULTS

Group A rabbits showed no atherosclerosis, whereas Group B rabbits had 17.4 +/- 9.3% (mean +/- SD) of the aorta covered with atherosclerosis, and Groups C, D and E rabbits had significantly less atherosclerosis. Plasma SOD activity was lower in Group B than in Group A (6.9 +/- 1.1 vs. 12.8 +/- 1.5 U/ml, p < 0.01) and was preserved in the groups given lovastatin, vitamin E or amlodipine with a high cholesterol diet. The serum MDA level was higher in Group B rabbits than Group A rabbits (12.1 +/- 2.6 vs. 1.2 +/- 0.1 nmol/ml, p < 0.01) and increased minimally in rabbits given lovastatin, vitamin E or amlodipine with a high cholesterol diet. In in vitro experiments, both lovastatin and amlodipine preserved SOD activity and reduced the oxidizability of low density lipoproteins by rabbit leukocytes.

CONCLUSIONS

This study suggests that a reduction in lipid peroxidation and preservation of SOD may be common mechanisms of antiatherosclerotic effects of lovastatin, vitamin E and amlodipine.

摘要

目的

我们试图记录降胆固醇的羟甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂洛伐他汀、二氢吡啶类钙通道阻滞剂氨氯地平和抗氧化剂维生素E抗动脉粥样硬化作用的共同机制。

背景

维生素E、HMG-CoA还原酶抑制剂和钙通道阻滞剂均可抑制高胆固醇血症动物的动脉粥样硬化。

方法

将新西兰白兔分为五组，分别给予常规饲料（A组）、含1%胆固醇的饲料（B组）、含1%胆固醇饲料加洛伐他汀（C组）、含1%胆固醇饲料加维生素E（D组）或含1%胆固醇饲料加氨氯地平（E组），喂养12周。通过对嗜苏丹区域进行平面测量来测定主动脉粥样硬化的程度。分别测定血液中的丙二醛（MDA）和超氧化物歧化酶（SOD）水平，作为脂质过氧化和抗氧化活性的指标。

结果

A组兔子未出现动脉粥样硬化，而B组兔子主动脉有17.4±9.3%（平均值±标准差）被动脉粥样硬化覆盖，C、D和E组兔子的动脉粥样硬化程度明显较轻。B组血浆SOD活性低于A组（6.9±1.1对12.8±1.5 U/ml，p<0.01），而在给予高胆固醇饮食并同时服用洛伐他汀、维生素E或氨氯地平的组中SOD活性得以保留。B组兔子血清MDA水平高于A组兔子（12.1±2.6对1.2±0.1 nmol/ml，p<0.01），而给予高胆固醇饮食并同时服用洛伐他汀、维生素E或氨氯地平的兔子血清MDA水平仅有轻微升高。在体外实验中，洛伐他汀和氨氯地平均可保留SOD活性，并降低兔白细胞对低密度脂蛋白的氧化能力。