一氧化氮及其合酶在家兔粥样硬化动脉的改变及L-精氨酸的作用  

Changes of Nitric Oxide and Nitric Oxide Synthases in Atherosclerotic Rabbit Aorta and Antiatherosclerotic Effect of L-Arginine

作　　者：徐少平[1] 李鲁光[1] 唐朝枢[2] 余燕秋[1] 沙鸥[1] 程友琴[1] 徐幼月[1] 

机构地区：[1]北京军区总医院心内科,北京100700 [2]北京医科大学心血管基础研究所

出　　处：《中国动脉硬化杂志》1999年第3期197-200,共4页Chinese Journal of Arteriosclerosis

基　　金：军队‘九.五’医药卫生科研基金

摘　　要：为探讨一氧化氮及其合酶在高胆固醇饮食诱导的动脉粥样硬化中的改变及 Ｌ－ 精氨酸的抗动脉粥样硬化作用，在高胆固醇饮食诱导的动脉粥样硬化模型上，检测了血清总胆固醇、血浆精氨酸、非对称性二甲基精氨酸和氧化型低密度脂蛋白浓度，主动脉一氧化氮合酶活性、一氧化氮生成量及内膜斑块面积。结果发现，高胆固醇饮食对血浆 Ｌ－ 精氨酸水平无明显影响，但血清总胆固醇、血浆非对称性二甲基精氨酸和氧化型低密度脂蛋白浓度显著升高，主动脉一氧化氮合酶活性及一氧化氮生成量分别较正常对照组降低４５ ％ 及３０ ％ （ Ｐ＜ ０ ．０１） ，内膜斑块面积达４２ ．６ ％ ±９ ．２ ％ 。口服 Ｌ－ 精氨酸虽无降低血清总胆固醇、血浆非对称性二甲基精氨酸和氧化型低密度脂蛋白浓度作用，但血浆 Ｌ－ 精氨酸浓度约升高一倍，主动脉一氧化氮合酶活性显著升高，一氧化氮生成量恢复正常（ Ｐ＜ ０ ．０１） ，内膜斑块面积减少至１９ ．５ ％ ±７ ．４ ％ （ Ｐ＜ ０ ．０５） 。结果提示，高胆固醇饮食诱导的动脉粥样硬化兔主动脉一氧化氮合酶－ 一氧化氮系统活性显著受损，动脉粥样硬化的发生发展与该系统活性受损密切相关。内源性一氧化氮生成减少是由于主动脉一氧化氮合酶活性降低所致。 Ｌ－ 精氨酸通?Aim To investigate the changes of aortic nitric oxide (NO) and NO synthases (cNOS and iNOS) in atherosclerotic rabbits induced by high cholesterol diet and the antiatherosclerotic effect of L-arginine. Methods Male New Zealand white rabbits were divided into three groups in random: the rabbits received either normal rabbit chow (normal group),1% cholesterol diet only (cholesterol group) or 1% cholesterol diet plus L-arginine (22.5% in drinking water, arginine group). Serum total cholesterol (TC), plasma L-arginine, asymmetric dimethlarginine (ADMA) and oxidized low density lipoprotein (ox-LDL) concentrations were detected. After 10 weeks, the aorta were harvested for assessment of NO production, NOS activities and area of intimal lesions. Results Compared with normal group, plasma L-arginine level had no significant alteration in cholesterol group, but serum TC, plasma ADMA and ox-LDL concentrations elevated markedly (P<0.01 or P<0.05). Aortic cNOS activity and NO production decreased about 45% and 30% respectively (P<0.01). Intimal lesions increased to 42.6%±9.2%. Compared with cholesterol group, dietary L-arginine had no effects on serum TC,plasma ADMA and ox-LDLconcentrations, but plasma L-arginine level increased about one time、aortic cNOS activity and NO production increased significantly (P<0.01). Intima lesion formation were inhibited markedly (19.5%±7.4% vs 42.6%±9.2%, P<0.05). Conclusions The activity of aortic NOS-NO system is impaired significantly in atherosclerotic rabbits induced by cholesterol diet. Progressive intimal lesion formation is associated with impaired activity of NOS-NO system. Decrease of cNOS activity results in reduction of NO production. L-arginine inhibits atherosclerotic progression by augmenting cNOS activity and restoring NO elaboration.

关 键 词：动脉粥样硬化 一氧化氮 精氨酸 

分 类 号：R543.5[医药卫生—心血管疾病]