阿托伐他汀对低密度脂蛋白受体基因敲除小鼠IL-17a、LP-PLA2表达的影响  

Impacts of atorvastatin on expression of IL-17a, LP-PLA2 in low-density lipoprotein receptor knockout mice

作　　者：倪云杰 林振浩 侯良磊 吴漪皓[1] 宋丽娟[1] 胡欢欢[1] 黄晓燕[2] 杨德业[1,2] 

机构地区：[1]温州医科大学附属第一医院心内科,浙江温州325015 [2]杭州师范大学附属医院心内科,浙江杭州310015

出　　处：《温州医学院学报》2015年第5期327-331,共5页Journal of Wenzhou Medical College

基　　金：国家自然科学基金资助项目(81270230)

摘　　要：目的:探讨阿托伐他汀对低密度脂蛋白受体基因敲除(LDLR-/-)小鼠白介素-17a(IL-17a)、脂蛋白相关磷脂酶A2(LP-PLA2)表达的影响。方法:取18只8周龄雄性LDLR-/-小鼠,12只给予高脂饮食(高脂饮食组)用于建立动脉粥样硬化模型,6只给予普通饮食作为普食对照组。8周后,将高脂饮食小鼠随机分成2组:高脂对照组(n=6)和治疗组(n=6,阿托伐他汀60 mg·kg-1·d-1灌胃),继续给予高脂饮食。8周后处死小鼠,全自动生化仪测血清血脂水平,HE染色观察斑块形态,q RT-PCR测主动脉中IL-17a和LP-PLA2的m RNA表达,免疫组织化学法测斑块中IL-17a的表达,Western blot法测主动脉中LP-PLA2的表达。结果:高脂对照组血清总胆固醇(TC)、低密度脂蛋白(LDL)含量均明显高于普食对照组(均P<0.05),甘油三酯(TG)含量两者差异无统计学意义(P>0.05)。治疗组与高脂对照组相比,血清TC、LDL含量明显降低(均P<0.05),TG含量两者差异无统计学意义(P>0.05)。高脂对照组小鼠主动脉组织内可见明显动脉粥样硬化斑块形成,斑块内IL-17a的平均吸光度值(MA)高于普食对照组(P<O.05)。治疗组与高脂对照组相比,斑块明显减少,斑块内IL-17a的MA也明显降低(P<0.05)。高脂对照组主动脉IL-17a和LP-PLA2的m RNA表达以及LP-PLA2蛋白的表达均高于普食对照组(均P<O.05)。治疗组与高脂对照组相比,主动脉IL-17a和LP-PLA2的m RNA以及LP-PLA2蛋白的表达均明显降低(均P<0.05)。结论:阿托伐他汀可降低LDLR-/-小鼠动脉粥样硬化模型中的血脂水平,可有效抑制IL-17a、LP-PLA2的表达,对抗动脉粥样硬化的作用。Objective： To investigate the effect of atorvastatin on expression of IL-17 a, LP-PLA2 in LDLRknockout（LDLR-/-） mice. Methods： Eighteen 8-week-old male LDLR-/- mice were raised in six cages. Twelve mice were fed with high fat diet for establishing atherosclerosis model. The other six mice were fed with normal diet which was used as the normal diet control group. After eight weeks, mice fed with high fat diet were divided into high fat diet control group（n=6） and atorvastatin group（n=6, 60 mg·kg^-1·d^-1 per gavage）. The other six mice fed with normal diet which was used as normal diet control group and continued to feed normal diet. All mice were sacrificed after eight weeks. Automatic Biochemical Analyzer was performed to measure serum lipid levels. Hematoxylin and eosin（HE） staining was used to observe the morphology of plaque. q RT-PCR was performed to analyze the level of expression of IL-17 a m RNA and LP-PLA2 m RNA. Immunohistochemistry was performed to analyze the expression of protein IL-17 a. Western blot was performed to analyze the expression of protein LP-PLA2. Results： Serum cholesterol（TC） and low density lipoprotein（LDL） levels were significantly higher in high fat diet control group than that in normal diet control group（both P〈0.05）, while there were no significantly difference of triglyceride（TG） level between two groups（P〉0.05）. TC and LDL levels of Atorvastatingroup compared with the high fat control group were significantly reduced（P〈0.05）. Also, there were no significantly difference of TG level between two groups（P〉0.05）. Obviously, Atherosclerosis lesion area was observed in high fat diet control group, while there was no atherosclerosis lesion observed in normal diet control group. The expression of IL-17a（both protein and mRNA） and LP-PLA2（both protein and mRNA） in high fat diet control group was significantly upregulated than that in the normal diet control group（all P〈0.05）. Compared with the high fat control grou

关 键 词：动脉粥样硬化 阿托伐他汀 白介素-17a 脂蛋白相关磷脂酶A2 

分 类 号：R541[医药卫生—心血管疾病]