阿托伐他汀联合L-4F对apoE缺失小鼠HDL功能及水平的影响  

The combination of atorvastatin and L-4F improve the anti-oxidant and anti-inflammatory properties of HDL to reduce atherosclerosis in ApoE knockout mice

作　　者：李鹏[1,2] 程诚[1] 毕明辉[1] 王月刚[1] 吴平生[1] 

机构地区：[1]南方医科大学南方医院心内科,广州510515 [2]中山大学附属第五医院内科,广东珠海519000

出　　处：《重庆医学》2015年第17期2338-2340,共3页Chongqing medicine

摘　　要：目的通过采用高脂饮食喂养apoE缺失(apoE-/-)小鼠建立动脉粥样硬化(AS)模型,比较阿托伐他汀联合载脂蛋白A-I(apoA-I)模拟肽(L-4F)对AS小鼠血清氧磷酯酶(PON1)、髓过氧化物酶(MPO)活性及血清低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平的影响。方法雄性apoE-/-小鼠50只,高脂饲料喂养作为模型组,另外取适龄C57BL/6J小鼠20只给予普通饲料喂养作为正常对照组,实验4周后,处死2组小鼠各10只,检测相应血清指标,作为基线参考。其余apoE-/-小鼠分为模型对照组(单纯高脂饮食)、阿托伐他汀组(高脂饮食基础上给予阿托伐他汀治疗)、L-4F组(高脂饮食基础上给予L-4F治疗)、阿托伐他汀联合L-4F组(高脂饮食基础上给予阿托伐他汀+L-4F治疗),每组10只。实验第8周末处死5组小鼠,并取小鼠血清检测各血清指标。结果实验第8周末,与模型对照组比较,各药物组血清PON1活性显著升高(均P<0.05),MPO活性显著下降(均P<0.05);与模型对照组比较,阿托伐他汀组、阿托伐他汀联合L-4F组LDL-C水平显著减低(P<0.05,P<0.01),HDL-C水平显著升高(P<0.05,P<0.01),L-4F组LDL-C、HDL-C水平差异无统计学意义(均P>0.05)。实验第8周末,阿托伐他汀联合L-4F组较阿托伐他汀组及L-4F组PON1活性、HDL-C水平显著升高(均P<0.05);MPO活性、LDL-C水平显著降低(均P<0.01)。结论阿托伐他汀、L-4F均可通过升高血清PON1活性,降低MPO活性,从而改善HDL抗氧化、抗炎功能,延缓AS进展。L-4F对LDL-C、HDL-C水平无影响。阿托伐他汀联合L-4F不仅降低LDL-C,升高HDL-C,而且更有效的改善HDL抗氧化、抗炎功能,从而延缓AS进展,优于单药使用。Objective To study the effect of atorvastatin combination with L-4Fon anti-oxidant and anti-inflammatory properties of high density lipoprotein（HDL）in apoE-/-mice fed with high-fat diet.Methods Fifty 8-week old male apoE-/-mice were fed with high-fat diet,while twenty 8-week old male C57BL/6Jmice were given normal diet as normal control group.4weeks later,10 mice in each group were sacrificed.The rest apoE-/-mice were randomly divided into 4groups：atherosclerosis（AS）model group（fat diet）,atorvastatin group（atorvastatin treatment with high-fat diet）,L-4Fgroup（L-4Ftreatment with high-fat diet）,and atorvastatin combined with L-4Fgroup（received atorvastatin ＋ L-4Ftreatment with high-fat diet）,and each group has 10 mice.At the end of 8th week,10 mice were sacrificed in each group.The activity of PON1,MPO,LDL-C,and HDL-C in serum were detected.Results Atthe end of the 8th week,we got the following 4points：Compared with the AS model group,the activity of PON1 in each drug groups increased significantly（all P〈0.05）,while the activity of MPO decreased significantly（all P〈0.05）,And the levels of serum LDL-C decreased significantly（P〈0.05,P〈0.01）,while the levels of serum HDL-C increased significantly（P〈0.05,P〈0.01）in both atorvastatin group and atorvastatin combined with L-4Fgroup.No significant difference was found in LDL-C and HDL-C level between AS model group and L-4Fgroup（P〈0.05）.Compared with the atorvastatin group and L-4Fgroup,the activity of PON1 and the level of serum HDL-C in atorvastatin combined with L-4Fgroup increased significantly（all P〈0.05）,while the activity of MPO and the level of serum LDL-C decreased significantly（all P〈0.01）.Conclusion Atorvastatin and L-4Fcan improve the anti-oxidant and anti-inflammatory effects by up-regulating the activity of PON1 and reducing activity of MPO in serum to reduce atherosclerosis.L-4Fdidn′t inflence the level of LDL-C and HDL-C in serum.The atorvastatin combined with L-4Fnot only can be mo

关 键 词：阿托伐他汀 动脉粥样硬化 L-4F 脂蛋白类 脂蛋白 HDL 

分 类 号：R965[医药卫生—药理学]