组蛋白乙酰化修饰在2种不同方法建立小鼠心肌肥厚模型中的作用  

The effects of histone acetylation modification on cardiac hypertrophy induced by two different modeling methods in mice

作　　者：罗孝美[1] 车建霖 刘诗如 龙珊 赵培希 许盼 魏燕 彭昌[3] 

机构地区：[1]遵义医学院基础医学院生理教研室,贵州遵义563000 [2]遵义医学院第一临床学院临床系 [3]遵义医学院附属医院儿内一科

出　　处：《临床心血管病杂志》2017年第11期1106-1110,共5页Journal of Clinical Cardiology

基　　金：国家自然科学基金项目(No:81560040);遵义医学院博士启动基金项目[院字(2015)4号];遵义医学院医学与科技学院大学生创新训练项目[遵医科院(2015)3108]

摘　　要：目的:探讨组蛋白乙酰化修饰失衡在2种不同方法建立小鼠心肌肥厚模型中的作用。方法:选取昆明小鼠为研究对象,按照随机数字表法随机分为5组:正常组、0.9%氯化钠溶液组、苯肾上腺素组、手术组和假手术组。苯肾上腺素组给予苯肾上腺素皮下注射,手术组给予部分结扎腹主动脉建立小鼠心肌肥厚模型,实时荧光定量聚合酶链反应(real-time polymerase chain reaction,RT-PCR)检测心肌肥厚相关标志物心房利钠肽(atrial natriuretic peptide,ANP)及β-肌球蛋白重链(β-myosin heavy chain,β-MHC)mRNA表达水平,免疫印迹(western blot,WB)检测小鼠心肌组织中组蛋白H3赖氨酸残基9位乙酰化(H3K9ac)的表达,比色法检测心肌组织中组蛋白乙酰化酶(histone acetylases,HATs)、组蛋白去乙酰化酶(histone deacetylases,HDACs)活性,超声心动图观察小鼠心肌肥厚情况。结果:RT-PCR结果表明苯肾上腺素组、手术组小鼠心肌组织中ANP和β-MHC mRNA表达水平分别显著高于0.9%氯化钠溶液组、假手术组(P<0.05);超声心动图结果显示苯肾上腺素组、手术组小鼠室间隔厚度、左室前壁厚度分别显著高于0.9%氯化钠溶液组、假手术组(P<0.05),而左室舒张末期直径则分别显著低于0.9%氯化钠溶液组、假手术组(P<0.05)。Western blot及比色法结果显示:苯肾上腺素组、手术组小鼠心肌组织中组蛋白H3K9ac的乙酰化水平及HATs活性分别显著高于0.9%氯化钠溶液组、假手术组(P<0.05),而HDACs活性则分别显著低于0.9%氯化钠溶液组、假手术组(P<0.05)。结论:组蛋白乙酰化修饰失衡均参与了2种不同方式所致的小鼠心肌肥厚。Objective：To investigate the effects of histone acetylation modification imblance on cardiac hypertrophy caused by two different modeling ways in mice.Method：Kunming mice were divided into five groups according to random number table method：normal group,normal saline group,phenylephrine group,operation group and sham-operation group.Phenylephrine group were administered with phenylephrine,and partial abdominal aortic stenosis was performed in the operation group to establish the model of cardiac hypertrophy in mice.The mRNA expression of atrial natriuretic peptide（ANP）andβ-myosin heavy chain（β-MHC）were identified by RealTime PCR.Meanwhile,the protein expression of histone H3 K9 ac was determined by western blot.The activities of histone acetylases（HATs）and histone deacetylases（HDACs）were tested by colorimetry in the myocardial tissues of mice.Cardiac hypertrophy in the mice was observed by echocardiography.Result：The results of Real Time PCR showed that the mRNA expression of ANP andβ-MHC in phenylephrine group and operation group were increased significantly compared with relative control group（P〈0.05）,and echocardiography data showed that interventricular septum and left ventricular posterior wall thickness were apparently increased in phenylephrine group and operation group than that relative control group（P〈0.05）,but left ventricular end diastolic diameter was decreased significantly in the same samples（P〈0.05）.The results of western blot and colorimetry showed that the level of histone H3 K9 ac and the activity of HATs were increased significantly in phenylephrine group and operation group compared with relative control group（P〈0.05）,but the activity of HDACs was decreased apparently in the same samples（P〈0.05）.Conclusion：The imbalance of histone acetylation modification was involved in cardiac hypertrophy induced by two different modeling ways.

关 键 词：心肌肥厚 模型 组蛋白乙酰化 小鼠 

分 类 号：R541.7[医药卫生—心血管疾病]