联合用药对动脉粥样硬化大鼠的作用机制  

Mechanism of combined use of drugs on atherosclerosis rats

作　　者：陈益民[1] 李玲[2] 曾艳萍 姚晨平[3] CHEN Yimin;LI Ling;ZENG Yanping;YAO Chenping(Department of Cardiology,the 421Hospital of PLA ,Guangzhou,Guangdong510310,China)

机构地区：[1]中国人民解放军第421医院心血管内科,广东广州510310 [2]中国人民解放军第421医院康复医学科,广东广州510310 [3]中国人民解放军第421医院门诊部,广东广州510310

出　　处：《中国热带医学》2018年第12期1194-1198,共5页China Tropical Medicine

摘　　要：目的研究普伐他汀钠和阿司匹林联合用药治疗动脉粥样硬化(AS)大鼠的作用机制,为临床用药提供依据。方法将SD雄性大鼠随机分为4组即正常组、模型组、普伐他汀钠组、普伐他汀钠联合阿司匹林给药组(联合组)。以高脂饲料方法制备AS大鼠模型,普伐他汀钠组大鼠灌胃给药剂量为0.3mg/(kg·d),联合组大鼠灌胃普伐他汀钠、阿司匹林剂量分别为0.3mg/(kg·d)、0.2mg/(kg·d),正常组、模型组给予普伐他汀钠组同体积的生理盐水,均治疗1个月。治疗后测定各组大鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、氧化型低密度脂蛋白(OX—LDL)、活性氧族(ROS)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH—Px)、丙二醛(MDA)、细胞间黏附分子-1(ICAM-1)、血管细胞黏附分子-1(VCAM-1)的含量。采用HE染色法观察大鼠主动脉病理变化,Western blot法检测大鼠主动脉LDL—R的蛋白表达情况。结果模型组血液中TC、TG、LDL、ox-LDL、MDA、ROS和ICAM-1、VCAM-1含量较正常组与给药组均升高,SOD及GSH—Px表达较正常组与给药组均降低。通过HE染色发现正常组大鼠比模型组大鼠血管中层平滑肌细胞增生,明显的泡沫状脂质颗粒沉积。而普伐他汀钠组、联合治疗组大鼠动脉壁内膜水肿逐渐消失,形态与正常组接近。经Western blot检测各给药组大鼠主动脉LDL—R蛋白表达显著低于模型组。结论联合用药在一定程度上比他汀类药物单一治疗AS造成的效果更佳。Objective To study the mechanism of combination of pravastatin sodium and aspirin in the treatment of atheroselerotie (AS)rats,and to provide the basis for clinical use.Methods SD male rats were randomly divided into four groups:normal group,model group,pravastatin sodium group,pravastatin sodium combined with aspirin group (combined group).With the method of high fat diet preparation of AS rat model,the pravastatin group rats were orally administered the dose of 0.3mg/(kg ·d);the combination group rats were orally administered pravastatin sodium,aspirin dose were 0.3mg/(kg·d),0.2mg/(kg,d),respectively;the blank group and model group were given saline pravastatin with the same volume of the sodium group,all patients were treated for 1months.The serum total cholesterol (TC),triglyeeride (TG),low density lipoprotein (LDL),high density lipoprotein (HDL),oxidized low density lipoprotein (ox-LDL),reactive oxygen species (ROS),superoxide dismutase (SOD)and glutathione peroxidase (GSH-Px),malondialdehyde (MDA),intercellular adh.esion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1)content of rats in each group after treatment were determined.The pathological changes of rat aorta were observed by hematoxylin -eosin (HE)staining,and the protein expression of aorta LDL-R in rat aorta was detected by Western blot.Results The levels of TC,TG,LDL,ox-LDL,MDA, ROS and ICAM-1 and VCAM-1 in the model group were higher than those in the normal group and the drug group,and the expressions of SOD and GSH-Px were lower than those in the normal group and the drug group.HE staining was used to observe the proliferation of smooth muscle cells in the middle layer of rat model group and the deposition of foamy lipid particles in the rats of the normal group.In the pravastatin sodium group and the combined treatment group,the arterial wall edema disappeared and the morphology was close to normal.The expression of LDL-R protein in aorta of each group was significantly lower than that of the model group by Western blot test.Con

关 键 词：动脉粥样硬化 作用机制 黏附因子 普伐他汀钠 联合用药 

分 类 号：R543.5[医药卫生—心血管疾病]