内源性一氧化氮及一氧化碳的改变对家兔动脉粥样硬化进程的影响  

Influence of changes of endogenous nitric oxide and carbon monoxide on atherosclerotic process in rabbits

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

机构地区：[1]北京军区总医院心内科,100700 [2]北京大学医学部心血管基础研究所

出　　处：《中华心血管病杂志》2001年第3期181-183,共3页Chinese Journal of Cardiology

基　　金：军队‘九五’医药卫生科研课题 (95B0 15 )

摘　　要：目的　探讨主动脉内源性一氧化氮 (NO)及一氧化碳 (CO)在高胆固醇饮食诱导的动脉粥样硬化 (AS)中的变化及对AS进程的影响。方法　家兔予以高胆固醇饮食 (胆固醇组 ,n =7)以及在高胆固醇饮食的同时经饮水给予L 精氨酸 (精氨酸组 ,n =9)或腹腔注射血红素 L 赖氨酸盐 (血红素组 ,n =9) ,共 10周。结果　高胆固醇饮食对血浆L 精氨酸水平无明显影响 ,但显著升高血清总胆固醇、血浆非对称性二甲基精氨酸及ox LDL浓度。与对照组 (n =6 )比较 ,胆固醇组主动脉NO及CO生成量显著减少 ,NO合成酶 (cNOS)及血红素加氧酶 (HO)活性显著降低 (P均 <0 .0 1) ,主动脉斑块面积达 (4 2 .6± 9.2 ) %。与胆固醇组比较 ,外源性L 精氨酸显著升高血浆L 精氨酸水平及主动脉cNOS活性 ,增加NO生成量 (P均 <0 .0 1) ,主动脉斑块面积仅 (19.5± 7.4) % (P <0 .0 5 ) ;外源性血红素 L 赖氨酸盐恢复了主动脉CO生成量 (P <0 .0 1) ,主动脉斑块面积为 (2 8.4± 8.1) % (P <0 .0 5 )。结论　高胆固醇饮食诱导的AS显著损害了主动脉NOS/NO及HO/CO系统 ,内源性NO及CO生成量减少与AS的发生发展密切相关。L 精氨酸及血红素 LObjective To investigate the changes of endogenous nitric oxide (NO) and carbon monoxide (CO) in atherosclerosis induced by high cholesterol diet in rabbits and influence of NO and CO on the atherosclerotic process.Methods The rabbits received 1% cholesterol diet (Chol group, n =7) or 1% cholesterol diet plus L arginine (2.25% in drinking water, Arg group) or heme L lysinate (9 mg·kg -1 ·d -1 , ip., Heme group, n =9). After 10 weeks, blood sample were abstracted from ear central artery for biochemical assay, aorta were harvested for assessment of NO and CO production, NO synthases (cNOS) and heme oxygenase (HO) activities. Results High cholesterol diet did not alter plasma L arginine concentration, but serum total cholesterol (TC), plasma asymmetric dimethylarginine (ADMA) and ox LDL concentrations increased markedly (all P <0.01). Compared with contrast group, n =7, aortic NO and CO production, cNOS and HO activity decreased markedly (all P <0.01), the aortic plaques area was (42.6±9.2)% in Chol group. Compared with Chol group, exogenous L arginine increased plasma L arginine concentration, elevated aortic cNOS activity and NO production (all P <0.01), the aortic plaques area was (19.5±7.4)% ( P <0.05); exogenous heme L lysinate restored aortic CO production ( P <0.01), the aortic plaques area was (28.4±8.1)% ( P <0.05). Both L arginine and heme L lysinate did not decrease serum TC, plasma ADMA and ox LDL concentrations. Conclusion Aortic NOS/NO and HO/CO system are impaired significantly in atherosclerotic rabbits induced by high cholesterol diet. Decreases of endogenous NO and CO production are associated with atherosclerotic progression. Both L arginine and heme L lysinate inhibit atherosclerotic progression by increasing NO or CO production.

关 键 词：动脉粥样硬化 一氧化氮 内源性 高胆固醇饮食 

分 类 号：R543.5[医药卫生—心血管疾病]