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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 changes of HO-1 / CO and inducible nitric oxide synthase (iNOS) / nitric oxide (NO) in atherosclerosis (AS) , Interrelationship and impact on the AS process. Methods Rabbits were given high cholesterol diet (n = 8) and L-arginine (n = 8) or L-NAME (n = 8) Lysine (n = 8) or ZnPP-IX (n = 8) for 10 weeks. Results Compared with the control group, the production of NO in the aorta of cholesterol group was significantly decreased, the CO production was significantly increased, the activity of NOS was significantly decreased (P <0.01), the expression of HO-1 was increased, the area of aortic plaque was (40.2 ± 8.9) %. Compared with the cholesterol group, the plaque area of aortic intima-hemin-L-lysine group [(26.6 ± 9.2)%] was significantly reduced, and the formation of aortic CO and the expression of HO-1 were significantly (P <0.01), but NOS activity and NO production were significantly lower than those in normal control group (P <0.01), but there was no significant difference between them and cholesterol group (P> 0.05). Compared with cholesterol group, - Arginine significantly increased cNOS activity in aorta, increased NO production, aortic plaque area [(28.1 ± 7.7)%] was significantly reduced (P <0.01), while HO-1 expression and CO formation The normal control group was significantly increased compared with the cholesterol group was no significant difference (P> 0.05). Compared with cholesterol group, mRNA and protein expression of c-myc and c-fos in aortas of heme-L-lysine intervention group and L-arginine group were significantly decreased, while ZnPP group and L- NAME group, the difference was not statistically significant. Conclusions During the process of atherosclerosis, the HO / CO and NOS / NO systems show complementary and compensatory regulation. The heme oxygenase system may inhibit the development of AS lesions through the regulation and compensatory mechanism of NO and NOS .