L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.
L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.
复制标题
L-精氨酸可预防 LDL 受体敲除小鼠中的黄瘤发展并抑制动脉粥样硬化。
DOI：
10.1161/01.cir.95.2.430
复制
发表时间：
1997
期刊：
影响因子：
37.8
通讯作者：
Cannon,PJ
中科院分区：
文献类型：
--
作者：
Aji,W;Ravalli,S;Szabolcs,M;Jiang,XC;Sciacca,RR;Michler,RE;Cannon,PJ
研究背景在家族性高胆固醇血症动物模型--缺乏功能性低密度脂蛋白受体基因的4组小鼠(每组10只)上，研究了NO的抗动脉粥样硬化作用。第1组喂以普通饲料喂养。第2组至第4组喂食1.25%的高胆固醇饮食。方法与结果6个月后处死动物，用油红O染色进行平面法染色，并用抗组成型和诱导型一氧化氮合酶(ω)诱导型NOSS的抗体进行染色。在接受高胆固醇饮食的动物中，血浆胆固醇显著增加。所有单独喂食高胆固醇饮食的小鼠都出现了黄色素瘤，而服用1-精氨酸的小鼠则没有。所有服用高胆固醇饮食的小鼠都出现了动脉粥样硬化。与仅接受高胆固醇饮食的小鼠相比，给予精氨酸的高胆固醇饮食小鼠的平均动脉粥样硬化病变面积显著减少(P<；.01)。服用L-精氨酸+L-NA的高胆固醇饮食小鼠的平均动脉粥样硬化病变面积显著大于单纯高胆固醇饮食小鼠(P<；.01)。在动脉粥样硬化斑块内，内皮细胞表达内皮细胞一氧化氮合酶；巨噬细胞、泡沫细胞和平滑肌细胞表达诱导型一氧化氮合酶和硝基酪氨酸残留物。结论L-精氨酸可预防高胆固醇饮食低密度脂蛋白受体基因敲除小鼠黄瘤的形成，减轻动脉粥样硬化。L-精氨酸的有益作用被L-那取消，提示L-精氨酸的抗动脉粥样硬化作用是通过一氧化氮合酶介导的。这些数据表明，l-精氨酸可能对家族性高胆固醇血症有益。
BackgroundThe potential antiatherosclerotic actions of NO were investigated in four groups of mice (n=10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplementall-arginine and group 4 receivedl-arginine andNω-nitro-l-arginine (L-NA), an inhibitor of NO synthase (NOS).Methods and ResultsAnimals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receivingl-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P<.01) in the cholesterol-fed mice givenl-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P<.01) in cholesterol-fed mice receivingl-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues.ConclusionsThe data indicate thatl-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects ofl-arginine by L-NA suggests that the antiatherosclerotic actions ofl-arginine are mediated by NOS. The data suggest thatl-arginine may be beneficial in familial hypercholesterolemia.