动脉粥样硬化形成过程中内源性一氧化碳和一氧化氮的变化及其相互关系

目的 研究食饵性动脉粥样硬化(AS)形成过程中,主动脉内源性一氧化氮(NO)及一氧化碳(CO)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(胆固醇组,n=8),同时经腹腔注射氯化血红素(血红素组,n=8)或锌原卟啉-9(卟啉锌组,n=8),或经饮水给予L-精氨酸(精氨酸组,n=8)或亚硝基-L-甲酯(亚硝基组,n=8),共12 w.结果 高胆固醇饮食显著升高血清脂质[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL)、氧化型LDL(ox-LDL)]水平,与对照组比较,胆固醇组主动脉NO生成量及NO合成酶(cNOS)活性明显降低,CO生成量及HO活性明显增加(均P<0.01),主动脉斑块面积为(54.00±4.16)%.与胆固醇组比较,氯化血红素显著增加HO活性及CO生成量,主动脉斑块面积仅(17.88±3.01)%(均P<0.01);卟啉锌显著降低HO活性及CO生成量,主动脉斑块面积高达(61.13±3.50)%(均P<0.01);L-精氨酸显著增加cNOS活性及NO生成量,主动脉斑块面积仅(18.57±3.49)%(均P<0.01);亚硝基-L-精氨酸甲酯显著降低cNOS活性及NO生成量,主动脉斑块面积高达(56.72±3.66)%(均P<0.01).结论 高胆固醇饮食诱导的AS使主动脉NOS/NO系统显著受损,HO/CO与NOS/NO两系统显示互补及代偿性调节作用,HO/CO系统通过对NOS及NO的调节和代偿从而抑制AS进展.

Change and correlation of endogenous carbon monoxide and nitric oxide in atherosclerotic process of rabbits

Objective To study the change of endogenous carbon monoxide (CO) and nitric oxide ( NO) in rabbit aorta with ather-osclerosis( AS) induced by high cholesterol diet and the inffluence of CO and NO on AS process. Methods The rabbits were given 1. 5% cholesterol diet (Ch group) or 1.5% cholesterol diet plus hemin (15 mg · kg~(-1)·d~(-1), ip. , Hm group) or zincprotoporphyrin IX (Znpp-IX, 45 μmol · kg~(-1)·d~(-1) , ip. , Zn group) or L-arginine(2. 25% in drinking water, Arg group) or L-nitro-arginine methylester(0. 12% in drinking water, L-NAME group), each group had 8 rabbits. After 12 w, the levels of serum lipids(TC, TG, LDL-C, HDL-C, ox-LDL) and the contents of aortic CO and NO,NO synthases(cNOS) and heme oxygenase( HO) activity were assessed, the aortic AS was measured by image analyse system. Results High cholesterol diet markedly enhanced the levels of serum TC, TG, LDL-C and ox-LDL (all P < 0. 01 ) . Compared with those of control group, the contents of aortic NO and cNOS were decreased markedly, the content of CO and the activity of HO were increased markedly (all P <0. 01) in Ch group, and the aortic plaques area was (54.00 ±4. 16)%. Hemin injection increased markedly the activities of aortic HO and CO, the aortic plaques area was (17. 88 ±3. 01)%. Znpp-IX injection made the opposite results, the aortic plaques area was (61. 13 ±3. 50)%. L-arginine increased markedly the activities of aortic cNOS and CO, the aortic plaques area was (18. 57 ±3. 49)% , L-NAME made the opposite results, the aortic plaques area was (56. 72 ±3. 66)%. Conclusions Aortic NOS/ NO system are impaired significantly in AS rabbits. The reciprocal correlation of HO/CO and NOS/NO systems in AS could play the protective role against AS lesion.