血红素氧合酶1—一氧化碳和一氧化氮合酶1—一氧化氮系统在动脉粥样硬化中的作用及其相关性研究

目的探讨血红素氧合酶1-一氧化碳和诱生型一氧化氮合酶-一氧化氮在动脉粥样硬化中的变化、相互关系及对动脉粥样硬化进程的影响. 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-亚硝基精氨酸甲酯(n=8),或经腹腔注射血红素-L-赖氨酸盐(n=8)或锌原卟啉-9(n=8),共10周.结果与对照组比较,胆固醇组主动脉一氧化氮生成量显著减少,一氧化碳生成量则明显增加,一氧化氮合酶活性显著降低(P均<0.01),而血红素氧合酶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,主动脉一氧化碳的生成量和血红素氧合酶1的表达明显升高(P<0.01),但一氧化氮合酶活性和一氧化氮生成量较正常对照组显著降低(P<0.01),与胆固醇组比较则无显著性差异(P>0.05);与胆固醇组比较,外源性L-精氨酸组主动脉一氧化氮合酶活性显著升高, 一氧化氮生成量增加,主动脉斑块面积(28.1%±7.7%)明显缩小(P均<0.01),而血红素氧合酶1的表达和一氧化碳的生成较正常对照组明显升高,与胆固醇组比较则无显著性差异(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(P均<0.01),而锌原卟啉组和L-亚硝基精氨酸甲酯组则无明显差异.结论动脉粥样硬化进程中,血红素氧合酶/一氧化碳和一氧化氮合酶/一氧化氮系统显示出互补及代偿性调节作用,血红素氧合酶系统通过对一氧化氮和一氧化氮合酶的调节和代偿机制抑制动脉粥样硬化病变的发展.

Relationship Between Heme Oxygenase/Carbon Monoxide and Nitric oxide Synthase/Nitric Oxide System in Atherosclerotic Progress

Aim To investigate the change rule and correlation of carbon monoxide (CO)/heme oxygenase-1 (HO-1) and nitric oxide (NO)/nitric oxide synthase (NOS) system in atherosclerosis and the influence of the two systems on atherosclerotic progress. Methods The rabbits received 1% cholesterol diet (chol group, n=8)or 1% cholesterol diet plus L-arginine (L-arg group, n=8) or L-NAME (L-NAME group, n=8) by drinking water, or 1% cholesterol diet plus heme-L-lysinate (Heme group, n=8) 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 were decreased markedly; however, CO production and HO-1 activity were increased obviously (p<0.01). Compared with chol group (40.2%±8.9%), aortic plaque areas of heme group(26.6%±9.2%) was reduced distinctly while aortic CO production and NOS activity were increased obviously (p<0.01). However, compared with contrast group, HO-1 expression and CO production in heme group were decreased markedly (p<0.01) while they were not different from the chol group (p>0.05). Compared with chol group, aortic NOS activity and NO production of L-arg group were increased obviously and aortic plaques area (28.1%±7.7%) was reduced greatly (p< 0.01 ). HO-1 expression and CO production of L-arg group were increased distinctly compared with contrast group while they were not different from chol group (p>0.05). Compared with chol group, aortic c-myc and c-fos expression of both heme group and L-arg group were reduced markedly while in ZnPP and L-NAME group they were not different from chol group. Conclusions The reciprocal relationship between heme oxygenase/carbon monoxide and nitri coxide synthase/nitrogen monoxide system in atherosclerosis could play the inhibitory role against atherosclerotic lesion.