阿托伐他汀钙及福辛普利在小鼠颈动脉粥样硬化形成中的干预作用

Effects of Atorvastatin and Fosinopril on Atherosclerosis in Rats

目的探讨阿托伐他汀钙及福辛普利在高血脂症下对动脉粥样硬化的干预作用。方法 40只雌性C57BL/6小鼠,于左侧颈总动脉外置入鞘管后随机分为对照组、阿托伐他汀钙组[10mg/(kg.d)]、福辛普利组[50mg/(kg.d)]和联合用药组[阿托伐他汀钙10mg/(kg.d)+福辛普利50mg/(kg.d)]4组,每组10只。各组小鼠均术后当日饲以高脂饮食,用药组根据小鼠体质量通过饮水途径饲以相关药物,对照组未进行药物干预。观察12周后,进行血清学指标检测并取双侧颈动脉标本行HE染色。结果 HE染色可见对照组小鼠左侧颈总动脉有明显动脉粥样硬化形成,对照组小鼠左侧颈总动脉内膜中层厚度(IMT)明显高于阿托伐他汀钙组、福辛普利组和联合用药组[分别为(2.77±2.87)比(0.05±0.01)、(0.08±0.05)、(0.06±0.01)mm]。与对照组相比,阿托伐他汀钙能明显降低血清总胆固醇、低密度脂蛋白胆固醇(LDL-C)和巨噬细胞集落刺激因子(M-CSF)水平[总胆固醇(1.43±0.30)比(2.64±0.46)mmol/L;LDL-C(0.18±0.13)比(0.92±0.17)mmol/L;M-CSF(191.0±34.0)比(225.9±36.1)ng/L;均P<0.05],升高一氧化氮合酶(NOS)含量[(42.2±1.9)比(39.9±1.3)U/mL,P=0.01];与对照组比较,福辛普利组总胆固醇和LDL-C水平虽未见明显变化,但M-CSF和超氧化物歧化酶(SOD)水平明显降低[M-CSF(199.7±34.7)比(225.9±36.1)ng/L;SOD(40.6±10.2)比(50.7±3.8)U/mL;均P<0.05],NOS含量升高[(42.8±2.8)比(39.9±1.3)U/mL,P<0.01],两种药物联合应用未见明显协同效应(P>0.05)。结论阿托伐他汀钙及福辛普利均能抑制实验小鼠动脉粥样硬化的形成;两种药物联合应用未见明显协同作用。福辛普利较阿托伐他汀钙更能明显抑制小鼠体内氧化应激反应。

Objective To investigate the roles of atorvastatin and fosinopril on the atherosclerosis in rats.Methods After collars were placed around the left common carotid arteries,40 female C57BL/6 mice were divided into four groups：control,atorvastatin[10 mg/（kg·d）],fosinopril [50 mg/（kg·d）] and combination [atorvastatin 10 mg/（kg·d）＋ fosinopril 50 mg/（kg·d）].Drugs were administrated through drinking water based on the body weight.After receiving high cholesterol diet for 12 weeks,carotid arteries in both sides were taken for HE staining,and serum markers were detected.Results HE staining showed that in control mice,left common carotid artery has the formation of atherosclerosis.Compared with control group,serum total cholesterol（TC）,low-density lipoprotein cholesterol（LDL-C）and macrophage colony-stimulating factor（M-CSF）level were decreased in atorvastatin group [TC（1.43±0.30）vs（2.64±0.46）mmol/L;LDL-C（0.18±0.13）vs（0.92±0.17）mmol/L;M-CSF（191.0±34.0）vs（225.9±36.1）ng/L;all P0.05];and nitric oxide synthase（NOS）was increased [（42.2±1.9）vs（39.9±1.3）U/mL;P=0.01].Compared with the control group,although the serum TC and LDL-C level had no significant difference,M-CSF and superoxide dismutase（SOD）levels were significantly lower [M-CSF（199.7±34.7）vs（225.9±36.1）ng/L;SOD（40.6±10.2）vs（50.7±3.8）U/mL;all P0.05] and NOS was significantly higher in fosinopril group [（42.8±2.8）vs（39.9±1.3）U/mL,P0.01].Two drugs may inhibit the formation of atherosclerosis;but have no obvious synergies effect（P0.05）.Conclusion Both atorvastatin and fosinopril can inhibit the formation of atherosclerosis,and the effet of fosinopril was stronger than that of atorvastatin on inhibiting oxidative stress in vivo.