HO-1/CO与NOS/NO系统在动脉粥样硬化中的作用及其相关性研究  

Relationship between heme oxygenase/carbon monoxide and nitricoxide synthase/nitrogen monoxide system in atherosclerotic progress

作　　者：邓俊 向贵平 黄骥[2] 

机构地区：[1]重庆市第六人民医院心血管内科,400060 [2]第三军医大学西南医院心内科,重庆400038

出　　处：《重庆医学》2006年第23期2146-2148,2150,共4页Chongqing medicine

摘　　要：目的探讨血红素氧合酶-1(HO-1)/一氧化碳(CO)系统与诱生型一氧化氮合酶(iNOS)/一氧化氮(NO)在动脉粥样硬化(AS)中的变化、相互关系及对AS进程的影响。方法家兔予以高胆固醇饮食(n=8)以及在高胆固醇饮食的同时经饮水给予L-精氨酸(n=8)或L-NAME(n=8),或经腹腔注射血红素-L-赖氨酸盐(n=8)或ZnPP-Ⅸ(n=8),共10周。结果与对照组比较,胆固醇组主动脉NO生成量显著减少,CO生成明显增加,NOS活性显著降低(P<0.01),而HO-1表达升高,主动脉斑块面积达(40.2±8.9)%。与胆固醇组比较,外源性血红素-L-赖氨酸盐干预组的主动脉内膜斑块面积[(26.6±9.2)%]明显缩小,主动脉CO的生成量和HO-1表达明显升高(P<0.01),但NOS活性与NO产量较正常对照组显著降低(P<0.01),与胆固醇组比较差异无统计学意义(P>0.05);与胆固醇组比较,外源性L-精氨酸显著升高主动脉cNOS活性,增加NO生成量,主动脉斑块面积[(28.1±7.7)%]明显缩小(P均<0.01),而HO-1的表达和CO的生成较正常对照组显著升高,与胆固醇组相比差异无统计学意义(P>0.05)。与胆固醇组比较,血红素-L-赖氨酸盐干预组、L-精氨酸组的主动脉组织内c-myc及c-fos的mRNA和蛋白表达均显著降低,而ZnPP组和L-NAME组则差异无统计学意义。结论动脉粥样硬化进程中,HO/CO和NOS/NO系统显示出互补及代偿性调节作用,血红素氧合酶系统有可能通过对NO和NOS的调节和代偿机制抑制AS病变的发展。Objective To investigate the change rule and correlation of carbon monoxide（CO）/heme oxygenase-1 （HO-1） and nitrogen monoxide（N（））/nitrieoxide synthase（NOS） system in atherosclerosis and the influence of the two systems on atheroscleretie progress. Methods The rabbits received 1 % cholesterol diet（chol group, 8 cases）or 1 % cholesterol diet plus L arginine（L-arg group,8 cases） or L-NAME（L-NAME group,8 cases） by drinking water, or 1% cholesterol diet plus hemc-L-lysinate（Heme group,8 cases） or ZnPP IX （ZnPP group,n= 8） by injection in abdominal cavity for ten weeks. Results Compared with contrast group, in chol group, aortic NO production and expression of NOS decreased markedly; contrarily, CO production（P〈0.01） and HO-1 activity increased obviously. The aortic plaques area was （40.2±8.9）% in chol group. Compared with chol group, aortic areas of heme group[（26.6 ± 9.2）%] reduced distinctly while aortic CO production and NOS activity increased obviously（P〈 0.01）. However, compared with contrast group, HO-1 expression and CO production in heme group decreased markedly（P〈 0.01） while they were not different from the chol group（P〉0.05）. Compared with chol group, aortic eNOS activity and NO production of L arg group increased obviously and aortic plaques areal（28. 1±7.7）%] greatly redueed（P〈0. 01 ）. However, HO-1 expression and CO production of L-arg group decreased distinctly compared with contrast group while were not different from chol group （P〉0.05）. Compared with chol group, aortic e-mye and c-fos expression of both heme group and L-arg group reduced markedly while in ZnPP and UNAME group they were not different from chol group. Conclusion The reciprocal relationship between HO-1/CO and NOS/NO system in atherosclerosis may play the inhibitory role against atherosclerotic lesion.

关 键 词：动脉粥样硬化 一氧化氮 一氧化氮合酶 一氧化碳 血红素氧化酶(脱环) 

分 类 号：R543.5[医药卫生—心血管疾病]