不同剂量瑞舒伐他汀对动脉粥样硬化大鼠体内脂联素水平的影响

Effects of different doses of rosuvastatin on adiponectin levels in rats with atherosclerosis in vivo

目的 探讨瑞舒伐他汀对动脉粥样硬化大鼠体内脂联素（APN）水平的影响及其剂量相关性.方法 40只SD雄性大鼠随机分为正常对照组（Con）、模型组（M）、高剂量喂药＋模型组（HD）、低剂量喂药＋模型组（LD）,其中模型组给予高脂饮食建立动脉粥样硬化模型.酶联免疫吸附试验（ELISA）法检测不同时段APN、一氧化氮（NO）、高敏C反应蛋白（hsCRP）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、总三酰甘油（TG）等水平的变化;同时取各组大鼠降主动脉进行病理切片,倒置差相显微镜下观察其内膜的形态学变化.结果 （1）与Con组[APN：（154.7±3.6）μg/L;NO.（51.0 ±3.2） μmol/L,下同]比较,其余3组APN、NO水平均降低,差异有统计学意义（P＜0.05）,其中M组[（89.0±5.4）μg/L;（27.8 ±3.1）μmol/L]低于HD[（128.4 ±0.8）μg/L;（45.5±0.9） μmol/L]、LD组[（107.5±3.8）μg/L;（39.5±1.2） μmol/L,P＜0.05],LD组低于HD组（P＜0.05）,差异均有统计学意义.（2）与Con组比较,其余3组hsCRP、LDL-C、TC、TG水平均升高,差异均有统计学意义（P＜0.05）,其中M组高于HD、LD组（P＜0.05）,LD组高于HD组（P＜0.05）,差异均有统计学意义.（3）瑞舒伐他汀的使用剂量（LD：0.5 mg/kg HD：4 mg/kg）与APN的变化[LD：（107.5±3.8）μg/L;HD：（128.4 ±0.8）μ/L]呈正相关（r=0.395,P＜0.05）;（4）瑞舒伐他汀干预下,APN、NO变化呈正相关（r=0.42,P＜0.05）;（5）病理检查显示：HD、LD、M组动脉内膜均较Con组有不同程度的损伤,M组损伤最严重,LD组次之,HD组损伤最轻.结论 瑞舒伐他汀能提升动脉粥样硬化大鼠体内APN水平,且该作用存在量效关系,瑞舒伐他汀的抗动脉粥样硬化作用可能与其提升AS大鼠体内APN水平从而进一步提升NO水平相关.

Objective To investigate the effects of rosuvastatin on adiponectin （APN） levels in rats with atherosclerosis （AS）,and the dose-effect relationship.Methods Forty SD male rats were randomly divided into 4 groups：normal control group （Con）,AS model group （M）,high dose rosuvastatin （4 mg/kg） ＋ AS group （HD）,and low dose rosuvastatin （0.5 mg/kg） ＋ AS group （LD）.The rats were fed on high fat diet to establish the AS model.Enzyme linked immunosorbent assay （ELISA） was used to detect APN,nitric oxide （NO）,high sensitivity-C-reactive protein （hsCRP）,low density lipoprotein-cholesterol （LDL-C）,total cholesterol （TC）,triglycerides （TG） levels in different periods.The descending aorta was taken out from each group for morphological observation of the arterial intima changes under light microscope.Results （1） As compared with Con group [APN：（154.7 ±3.6） μg/L;NO：（51.0 ±3.2） μmol/L],APN and NO levels in M,HD and LD groups were all remarkably decreased （P 〈0.05）,those in LD group [（107.5 ± 3.8） μg/L;（39.5 ± 1.2） μmol/L] were remarkably lower than in HD group [（128.4 ±0.8） μg/L;（45.5 ±0.9） μmol/L,P〈0.05],and those in M group [（89.0±5.4） μg/L;（27.8 ±3.1） μmol/L] were remarkably lower than in LD group （P〈0.05）;（2） As compared with Con group,hsCRP,LDL-C,TC and TG levels in M,HD and LD groups were all remarkably increased （P 〈 0.05）,those in LD group were remarkably higher than in HD group （P 〈 0.05）,and those in M group were remarkably higher than in LD group （P 〈 0.05）;（3） The doses of rosuvastatin was positively correlated with the change of APN [（107.5 ± 3.8） μg/L for LD group,and （128.4 ±0.8） μg/L for HD group,r =0.395,P 〈0.05];（4） There was a significantly positive correlation between the change of APN and NO under the treatment with rosuvastatin （r =0.42,P 〈 0.05）;（5） Histological,the arterial intimal injury was mild in HD group,moderate in LD grou,and severe in M group,respectively.Conclusion Rosuvastatin does enhance the APN level in the body of AS rats,and there does exist dose-effect relationship.The anti-atherogenic function of rosuvastatin may be related to the increased APN levels in AS rats in vivo,further the increased NO level.