辛伐他汀对高脂血症大鼠氧化应激状态的干预研究

Protection of simvastatin against oxidative stress injury in hyperlipidemic rats

目的:观察高脂血症大鼠氧化应激状态的变化及辛伐他汀对它的影响.方法:40只雄性SD大鼠随机分组,对照组16只给予正常饮食,24只大鼠喂食高脂饲料(30g/kg胆固醇、2g/kg去氧胆酸钠、100g/kg猪油、1g/kg丙基硫氧嘧啶、867g/kg基础饲料)8wk后分为3组:模型8wk组(n=8),模型16wk组(n=8)继续喂饲高脂饲料,辛伐他汀组(n=8)喂饲高脂饲料并给予辛伐他汀(每日10mg/kg)混悬液灌胃,模型16wk组及对照组给予等体积生理盐水灌胃,各组自由饮水进食.实验8wk分别处死对照组及模型8wk组大鼠各8只.实验16wk处死各组动物.留取血清及左心室组织,测定血清总胆固醇(TC),甘油三酯(TG),戊二醛(MDA),谷胱苷肽过氧化物酶(GPx)及过氧化物歧化酶(SOD)活性.结果:与对照组相比,模型8wk组血清总胆固醇升高,血清及心肌组织MDA含量增加,GPx活性降低(P均<0.05),但甘油三酯及血清和心肌组织SOD活性没有统计学差异(P均>0.05);与模型8wk组相比,模型16wk组胆固醇和甘油三酯继续升高,血清及心肌组织MDA含量增加,SOD和GPx活性降低(P均<0.05);与模型16wk组相比,辛伐他汀组胆固醇和甘油三酯均降低(P均<0.05),血清及心肌组织MDA含量减少,SOD和GPx活性升高(P均<0.05).结论:高脂血症大鼠存在氧化应激,给予辛伐他汀可减轻氧化应激损伤,从而可能减缓动脉粥样硬化的形成.

AIM： To investigate whether simvastatin reduces oxidative stress injury in hyperlipidemic rats. METHODS： Male SD rats were randomly subjected to the following treatments： standard diet （ control group, n = 16）, high-fat diet （ containing 30 g/kg cholesterol, 2 g/kg sodium deoxycholate, 1 g/kg propyl- thyracil, 100 g/kg lard, and 867g/kg base feed） for 8 weeks （8- week-model group, n = 8） , high-fat diet for 16 weeks（ 16-weekmodel group, n = 8）, and high-fat diet plus orally administered simvastatin（ 10 mg/kg·d） from 8 to 16 weeks （simvastatin group, n = 8 ）. Control group and 16-week-model group were administered orally normal saline of equal volume instead. Triglyceride（ TG ） , serum total cholesterol （TC） , serum and myocardial malondialdehyde （ MDA）, glutathione peroxidase （GPx） , and superoxide dismutase（SOD） activity were detected after rats of each group were sacrificed, RESULTS： Compared with the control group, in 8-week-model group, serum TC and MDA increased, GPx decreased in the both serum and heart （ all P 〈 0.05）, and TG and SOD activity did not change significantly. Compared with the 8-week-model group, in 16-week-model group , TC TG and MDA increased and SOD and GPx activities decreased （ all P 〈 0.05）, Compared with the 16-week-model group, administration of simvastatin decreased TC, TG and MDA but increased SOD and GPx activities in the both serum and heart （ all P 〈 0.05 ）. CONCLUSION： Hyperlipidemia can lead to an oxidative stress injury, which can be reduced by the administration of simvastatin,