N-乙酰半胱氨酸预防兔实验性动脉粥样硬化的作用途径

Pathway of the role of N-acetylcystein in preventing experimental atherosclerosis in rabbits

目的：探讨N-乙酰半胱氨酸对兔实验性动脉粥样硬化预防作用的途径。 方法：实验于2004-08／12在锦州医学院科学实验中心实验室完成。选择健康日本大耳白兔24只，给予普通颗粒饲料喂养1周后，随机分为4组，正常对照组、模型组、N-乙酰半胱氨酸50mg／(kg·d)，150mg／(kg·d) 组各6只。①正常对照组：喂饲普通颗粒饲料。②模型组：用高脂饲料喂养，即在普通饲料中加入1g胆固醇和8g猪油。③N-乙酰半胱氨酸50mg／(kg·d)组：每只兔给予N-乙酰半胱氨酸50mg／(kg·d)，混合于与模型组同条件的高脂饲料中喂饲。④N-乙酰半胱氨酸150mg(kg·d)组：每兔给予N-乙酰半胱氨酸150mg／(kg·d)，其余同③。造模及预防性用药共10周，实验共11周。实验结束后分别检测各组兔的血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇、一氧化氮和内皮素，低密度脂蛋白胆固醇(mmol／L)=总胆固醇-高密度脂蛋白胆固醇-三酰甘油／2．2。实验结束后，麻醉处死动物，解剖后取主动脉行病理形态学观察并定量分析病变程度。 结果：纳入24只白兔全部进入结果分析，无脱失。①各组兔的血清血脂水平及一氧化氮、内皮素含量比较：喂饲高脂饲料后，模型组、N-乙酰半胱氨酸50mg／(kg·d)，150mg／(kg·d)组兔的血清中总胆固醇、三酰甘油、低密度脂蛋白胆固醇水平均显著高于正常对照组(P<0．01)，高密度脂蛋白胆固醇显著低于正常对照组(P<0．01)。但两用药组与模型组比较，差异无显著性意义(P>0．05)。N-乙酰半胱氨酸150mg／(kg·d)组兔的一氧化氮含量显著高于模型组和N-乙酰半胱氨酸50mg／(kg·d)组(P<0．01)，而N-乙酰半胱氨酸150mg(kg·d)组兔的内皮素含量显著低于模型组和N-乙酰半胱氨酸50mg／(kg·d)组(P<0．01)。②各组兔主动脉的病理形态学观察结果比较：模型组主动脉内膜表面不光滑，动脉管壁弹性下降，染色后橘红色斑块明显向管腔凸出，N-乙酰半胱氨酸50mg／(kg·d)组兔的主动脉管壁弹性较好，斑块凸出不明显。N-乙酰半胱氨酸150mg／(kg·d)组主动脉内膜仅有少量脂质斑点形成，大部分内膜光滑，弹性好。 结论：N-乙酰半胱氨酸可以有效抑制动脉粥样硬化的进一步发展，其可能作用途径为N-乙酰半胱氨酸能够降低血清内皮素水平，增加一氧化氮生成，从而减少血管内皮的氧化损伤，但此作用与血脂水平无关。

AIM： To investigate the action pathway of N-acetylcystein in preventing experimental atherosclerosis in rats. METHODS： The experiment was carried out in the scientific experimental central laboratory of Jinzhou Medical College between August and December 2004. Twenty-four healthy Japanese big-ear rabbits were fed with common forage for 1 week, and then randomly divided into four groups with 6 rabbits in each group： normal control group, model group, N-acetylcystein low and high dose （50 and 150 mg/kg per day） groups. ① normal control group： fed with common forage; ② model group： fed with high fat forage, common＋l g cholesterol＋8 g lard）; ③N-acetylcystein low dose group： fed with high fat forage plus N-acetylcystein 50 mg/kg per day; ④ N-acetylcystein high dose group： fed with high fat forage plus N-acetylcystein 150 mg/kg per day. The model establishment and preventive medication cost totally 10 weeks, and the experiment lasted for 11 weeks. At the end of the experiment, the levels of serum total cholesterol, triglyceride, high density lipeprotein cholesterol （HDL-C）, nitric oxide and endothelin were detected respectively, low density lipoprotein cholesterol （LDL-C）= total cholesierol-HDL-C-triglycefide/2.2. After the experiment, the rabbits were anesthetized and killed, aorta was taken after dissection for observation of pathomorphology and quantitative analysis of the severity. RESULTS： All the 24 rabbits were involved in the analysis of results without deletion. ① Comparison of the levels of serum lipids and contents of nitric oxide and endothelin： After the rabbits were fed with high fat forage, the levels of serum total cholesterol, triglyceride and LDL-C in the model group, N-acetylcystein low and high dose groups were significantly higher than those in the normal control group （P 〈 0.01）, HDL-C was remarkably lower than that in the normal control group （P 〈 0.01）, but there were insignificant differences between the two medication groups and the model group （P 〉 0.05）. The content of nitric oxide was significantly higher in the N-acetylcystein high dose group than in the low dose group and model group （P 〈 0.01）, but the content of endothelin was significantly lower in the N-acetylcystein high dose group than in the low dose group and model group （P 〈 0.01）. ② Comparison of the aortic pathomorphology： In the model group, the surface of aortic tunica intima was not smooth and glossy, the elasticity of arterial canal wall was decreased, orange plaques after staining obviously evaginated towards the vascular chamber. In the N-acetylcystein low dose group, the elasticity of arterial canal wall was better, evagination of plaque was not obvious. In the N-acetylcystein high dose group, only a small amount of lipid lotch formed in aortic tunica intima, most of the intima was smooth and glossy with good elasticity. CONCLUSION： N-acetylcystein can effectively inhibit the further development of atherosclerosis by its effect in decreasing the level of serum endothelin, and increasing the production of nitric oxide, and then reduces the oxidative injury of vascular endothelium, but it has nothing to do with blood lipids.