自制α-硫辛酸缓释片对氧化低密度脂蛋白致兔实验性动脉粥样硬化的影响

背景：由于硫酸锌半衰期短，必须多次给药，所以临床常用针剂剂型患者依从性差。 目的：利用食饵性兔动脉粥样硬化模型观察自制α-硫辛酸口服缓释片对动脉粥样硬化的预防作用及其可能途径。 设计、时间及地点：随机对照动物实验，于2008-05/09在南方医科大学珠江医院中心实验室完成。 材料：24只新西兰大白兔喂养1周后随机分成3组，分别为正常组、模型组、硫辛酸组，每组8只。 方法：正常组喂饲普通颗粒饲料。模型组用高脂饲料喂养，即在普通饲料中加入1 g胆固醇和8 g猪油。硫辛酸组用高脂饲料喂养，另外每只兔通过胃管给予自制硫辛酸缓释片300 mg/d。喂饲高脂饲料及预防性用药12周。 主要观察指标：实验结束后分别检测各组血清三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、丙二醛、超氧化物歧化酶、氧化低密度脂蛋白、一氧化氮及内皮素1水平。 结果：①纳入24只兔全部进入结果分析，无脱失。②喂饲高脂饲料后，模型组血清中总胆固醇、三酰甘油、低密度脂蛋白胆固醇、丙二醛、氧化低密度脂蛋白及内皮素1水平均显著高于正常对照组(P < 0.05), 高密度脂蛋白胆固醇、超氧化物歧化酶及一氧化氮水平显著低于正常对照组(P < 0.05)。③硫辛酸组血清中总胆固醇、三酰甘油、低密度脂蛋白胆固醇、丙二醛、氧化低密度脂蛋白及内皮素1水平均显著低于模型组(P < 0.05)。硫辛酸组超氧化物歧化酶及一氧化氮水平高于模型组(P < 0.01)。 结论：自制α-硫辛酸缓释片具有预防动脉粥样硬化的作用，其机制可能与其清除超氧阴离子等自由基，减轻氧化低密度脂蛋白对血管内皮细胞的氧化损伤有关。

Effects of self-made sustained-release alpha-lipoic acid tablet on oxidized low density lipoprotein-induced rabbit experimental atherosclerosis

BACKGROUND: Zinc sulfate with short half-life period should be repeatedly administrated. Thus, patients undergoing injection had bad compliance. OBJECTIVE: To ascertain the pathway of the role of sustained-release alpha-lipoic acid tablet in preventing experimental atherosclerosis utilizing rabbit dietary atherosclerosis models. DESING, TIME AND SETTING: The randomized, controlled, animal study was performed at the Center Laboratory, Zhujiang Hospital, Southern Medical University from May to September 2008. MATERIALS: A total of 24 New Zealand rabbits following 1 week of feeding were randomized into 3 groups: normal group, model group and lipoic acid group. METHODS: Rabbits in the normal group were fed with common feed. Rabbits in the model group were treated with high fat feed (common feed + 1 g of cholesterol and 8 g of pork fat). Rabbits in the lipoic acid group were administered with high fat feed. Each rabbit was treated with self-made lipoic acid extended action tablet (300 mg/d) by a gastric canal. The model establishment and preventive medication spent totally 12 weeks. MAIN OUTCOME MEASURES: At the end of the experiment, the levels of serum total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, malondialdehyde, superoxide dismutase, nitric oxide, endothelin-1 and oxidized low density lipoprotein were detected respectively in each group. RESULTS: All the 24 rabbits were included in the final analysis, without drop-outs. After the rabbits were fed with high fat forage, the levels of serum total cholesterol, triglyceride, low density lipoprotein cholesterol, malondialdehyde, oxidized low density lipoprotein and endothelin-1 in the model group were significantly higher than in the normal group (P < 0.05), but high density lipoprotein cholesterol, superoxide dismutase and nitric oxide were significantly lower than in the normal group (P < 0.05). The levels of serum total cholesterol, triglyceride, low density lipoprotein cholesterol, malondialdehyde, oxidized low density lipoprotein and endothelin-1 in the lipoic acid group were significantly lower than in the model group (P < 0.05). The levels of serum superoxide dismutase and nitric oxide in the lipoic acid group were significantly higher than in the model group (P < 0.01). CONCLUSION: Self-made sustained-release alpha-lipoic acid tablet can prevent atherosclerosis. Its mechanism may be associated with scavenging free radicals such as superoxide anion and with relieving oxidative damage of oxidized low density lipoprotein on vascular endothelial cells.