摘要
目的:研究阿托伐他汀与一氧化碳供体分子3(CORM-3)联用对动脉粥样硬化(AS)易损斑块模型大鼠炎症及氧化应激指标的影响。方法:取大鼠随机分为对照组(灌胃生理盐水)、模型组(灌胃生理盐水)、他汀组[灌胃阿托伐他汀2 mg/kg]、他汀+CORM-3组[灌胃阿托伐他汀2 mg/kg+腹腔注射CORM-3 10 mg/kg],每组8只。对照组大鼠予以基础饲料喂养,右颈总动脉只经历手术暴露但不予损伤并用生理盐水代替药物干预;其余3组大鼠均予以高脂饲料喂养+右颈总动脉损伤+异种蛋白注射刺激免疫炎症反应等方法复制AS易损斑块模型,继续饲养10周后,给予相应药物进行干预,每天1次,连续2周。末次给药24 h后取腹腔动脉血,使用全自动生化分析仪测定血浆中低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)浓度,采用酶联免疫吸附试验检测血浆中超敏C反应蛋白(hs-CRP)、白细胞介素10(IL-10)、单核细胞超化蛋白1(MCP-1)、基质金属蛋白酶9(MMP-9)水平,化学比色法测定血浆中丙二醛(MDA)、氧化修饰型低密度脂蛋白(ox-LDL)水平,Western blot法测定血红素氧合酶1(HO-1)蛋白表达水平,并取右颈总动脉在光镜下观察病理学变化。结果:与对照组比较,模型组大鼠LDL-C、hs-CRP、MCP-1、MMP-9、MDA、ox-LDL水平和HO-1蛋白表达水平均明显升高(P<0.05),HDL-C、IL-10水平均明显降低(P<0.05),右颈总动脉形成明显的易损斑块。与模型组比较,他汀组和他汀+CORM-3组大鼠LDL-C、hs-CRP、MCP-1、MMP-9、MDA、ox-LDL水平均明显降低(P<0.05),HDL-C、IL-10水平和HO-1蛋白表达水平均明显升高(P<0.05),其中除LDL-C、HDL-C外其余指标他汀+CORM-3组改善效果较他汀组更明显(P<0.05),他汀组颈动脉斑块改变尚不明显,但他汀+CORM-3组AS病变较模型组和他汀组显著减轻,斑块结构也更趋稳定。结论:阿托伐他汀与CORM-3联用对AS易损斑块模型大鼠炎症及氧化应激指标的改善作用强�
OBJECTIVE:To study the effects of atorvastatin combined with carbon monoxide releasing molecule 3(CORM-3)on inflammation and oxidative stress indexes in atherosclerotic(AS)vulnerable plaque model rats.METHODS:The rats were randomly divided into control group(normal saline,i.g.),model group(normal saline,i.g.),statin group(atorvastatin 2 mg/kg,i.g.),and statin+CORM-3 group(atorvastatin 2 mg/kg,i.g.+CORM-3 10 mg/kg,i.p.),with 8 rats in each group.Control group was fed with basal diet,and the right common carotid artery was exposed to surgery without injury and was treated with normal saline instead of drug;other three groups were fed with high-fat diet+right common carotid artery injury+heteroprotein injection to induce AS vulnerable plaque model,for 10 weeks;and then they were given relevant medicine for intervention,once a day,for consecutive 2 weeks.24 h after last medication,abdominal artery blood was collected;the concentration of LDL-C and HDL-C were determined by fully automatic biochemical analyzer.The levels of hs-CRP,IL-10,MCP-1 and MMP-9 in plasma were detected by ELISA;plasma levels of MDA and oxidized low density lipoprotein(ox-LDL)were determined by chemical colorimetry;the protein expression of heme oxygenase-1(HO-1)was determined by Western blot.The pathological changes of right common carotid artery were observed under light microscope.RESULTS:Compared with control group,the levels of LDL-C,hs-CRP,MCP-1,MMP-9,MDA and ox-LDL,and protein expression of HO-1 were increased significantly(P<0.05),while the levels of HDL-C and IL-10 were decreased significantly in model group(P<0.05);the right common carotid artery formed obvious AS plaques.Compared with model group,the levels of LDL-C,hs-CRP,MCP-1,MMP-9,MDA and ox-LDL were decreased significantly in statin group and statin+CORM-3 group in model group(P<0.05),while the levels of HDL-C,IL-10 and the protein expression of HO-1 were increased significantly(P<0.05).Except for LDL-C and HDL-C,the improvement of other indexes in statin+CORM-3 group was more sig
作者
魏刚
包小敏
张英
黄维义
WEI Gang;BAO Xiaomin;ZHANG Ying;HUANG Weiyi(Dept.of Cardiology,the Affiliated Hospital of Southwest Medical University,Sichuan Luzhou 646000,China;Dept.of Functional Lab,Southwest Medical University,Sichuan Luzhou 646000,China)
出处
《中国药房》
CAS
北大核心
2019年第3期338-343,共6页
China Pharmacy
基金
四川省科技厅-泸州市人民政府-泸州医学院联合科研专项资金计划项目(No.14JC0051)
泸州市科技局项目(No.2013LZLY-J15)
