内源性HO-1/CO系统在动脉粥样硬化发病中的作用

Role of Endocrine HO-1/CO System in Atherosclerotic Progress

目的探讨血红素氧合酶-1(HO-1)/一氧化碳(CO)系统在动脉粥样硬化(AS)中的变化、对AS进程的影响及其可能的作用机制。方法家兔予以高胆固醇饮食以及在高胆固醇(n=8)饮食的同时经腹腔注射血红素-L-赖氨酸盐(n=8)或ZnPP-IX(n=8)共10周。结果与正常对照组比较,胆固醇饮食各组血清TC及ox-LDL显著升高(P均<0.01),但血清TC和ox-LDL在胆固醇组、ZnPP-IX组、血红素-L-赖氨酸盐干预组之间均无显著性差异。与对照组比较,胆固醇组主动脉CO生成量显著增加,HO-1表达升高(P均<0.01),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(P<0.01),主动脉HO-1表达及CO的生成量显著升高;与胆固醇组比较,血红素-L-赖氨酸盐干预组的主动脉组织内c-myc及c-fos的mRNA和蛋白表达均显著降低(P均<0.01),而ZnPP组与胆固醇组之间则无明显差异。结论HO-1/CO系统具有抗动脉粥样硬化作用,这种作用并非通过其对血浆TC及ox-LDL的调节实现,可能与该系统干预动脉组织内原癌基因表达从而抑制血管平滑肌细胞增殖有关。

Objective To investigate the change and role of carbon monoxide/heme oxygenase system in atherosclerosis and the possible role mechanism of the system in atherosclerotie progress. Methods The rabbits received 1% cholesterol diet（chol group, n = 8）or 1% cholesterol diet pins heme-L-lysinate（ Heine group, n = 8） or ZnPP-LX（ZnPP group, n = 8） by injection in abdominal cavity for ten weeks. Results Compared with control group, plasma levels of total cholesterol（TC） and oxide - low density lipoprotein（ox-LDL） increased obviously in all experimental groups. However, plasma levels of TC and ox-LDL were not much different among chol group, heme group and ZnPP group. Compared with control group, aortic CO production and HO-1 activity increased markedly （P 〈0. 01） in chol group. The aortic area was （40. 2 ± 8.9）% in chol group. Compared with chol group, aortic plaques areas of heme group[ （ 26. 6 ± 9. 2） % ] reduced distinctly while expression of HO-I and aortic CO producion increased ohviously（ P 〈 0.01）. Compared with ehol group, aortic c-myc and c-fos expression of heme group reduced markedly while in ZnPP group they were not different from ehol group. Conclusion Heine oxygenase/carbon monoxide system in atherosclerosis could play the inhihitory role against atherusclerotic lesion. The role is not carried out hy Heme oxygenase/carbon monoxide system which regulates plasma total cholesterol and ox-LDL , hut is related to the system that intervenes expression of oncogene and inhibits the proliferation of vascular smooth muscle cells.