舒降之、普罗布考、开搏通和祛淤消斑胶囊对食饵性兔动脉粥样硬化血管内皮舒缩功能的影响

The Effect and Mechanism of Simvastatin, Probucal, Captopril and Chinese Medicine on Vascular Endothelium Function

探讨舒降之、普罗布考、开搏通和祛淤消斑胶囊对食饵性兔动脉粥样硬化内皮依赖性血管扩张功能的影响及可能的机制。兔饲以 1%胆固醇饲料 12周 ,造成动脉粥样硬化 ,分别给予以上药物 ,12周后超声技术测量腹主动脉内皮依赖性血管扩张反应 ,检测血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇、丙二醛、超氧化物歧化酶、一氧化氮及血浆内皮素等 ,逆转录多聚酶链反应测量血管组织内皮素 1、诱导型一氧化氮合酶和血管紧张素转换酶的基因表达。 4种药物减轻乙酰胆碱血管收缩作用的效果依次为普罗布考、舒降之、祛瘀消斑胶囊和开搏通 ;总胆固醇和动脉内膜中层厚度与乙酰胆碱注射后动脉内径变化率均为中度负相关关系 (r分别为 - 0 .5 7、- 0 .4 7)。正常兔诱导型一氧化氮合酶、内皮素 1和血管紧张素转换酶在正常组有微量表达 ,动脉粥样硬化模型组升高分别达2 .5 6倍、7.6 0倍和 2 .6 7倍 ,在自然消退组内皮素 1和诱导型一氧化氮合酶继续轻度增高 ,而血管紧张素转换酶基因表达有轻度下降 ;与动脉粥样硬化模型组比较 ,普罗布考和开搏通降低诱导型一氧化氮合酶表达量达到显著性水平 ,普罗布考、开搏通和祛瘀消斑胶囊均显著降低血管紧张素转换酶表达 ,各服药组内皮素 1表达减弱。实验提示4种药物均可显著改善动脉粥样?

Aim To evaluate the therapeutic effects of simvastatin,probucal,captopril and chinese medicine on endothelium function of atherosclerosis(As). Methods The rabbits of As were given simvastatin, probucal, captopril and chinese medicine respectively for 12 weeks. The blood were drawn for measuring the lipids,malondialdehyde, superoxide dismutase, nitric oxide and endothelin 1 (ET 1). The endothelium dependent vascular relaxation (EDVR) of abdominal aorta was examinaed by injecting acetylcholine (Ach). The mRNA expression of inducible nitric oxide synthease (iNOS), ET 1, angiotensin converting enzyme (ACE) of As were examined by reverse transcription polymerase chain reaction. Results The aortic contraction caused by Ach decreased in probucal, simvastatin, chinese medicine and captopril groups than regression control group. Both total cholesterol and intima medial thickness showed negative correlations with EDVR(r=-0.57,0.47 respectively). In normal group, mRNA of iNOS, ET 1 and ACE were expressed in low levels. In comparison with regression control group, mRNA expression of iNOS,ET 1 and ACE in 4 drug therapy groups decreased, iNOS in probucal and captopril groups and ACE in probucal, captopril and chinese medcine groups reduced. Conclusion The 4 drugs can improve the EDVR disfunction in atherosclerosis and probucol has the best effect. EDVR improvement may be associated with the mechanisms of reducing expression of iNOS, ET 1 and ACE genes, and reduction of lipid peroxide.