早期氯沙坦干预对自发性高血压大鼠心肌中血管紧张素Ⅱ1型受体b亚型和血管紧张素Ⅱ1型受体相关蛋白基因甲基化的影响  

The effect of early losartan treatment on methylation of angiotensin Ⅱ type 1 receptor subtype b and angiotensin Ⅱ type 1 receptor associated protein gene in the myocardium of spontaneously hypertensive rats

作　　者：王庭俊[1] 林旭[1] 练桂丽 钟鸿斌[1] 谢良地[1] 

机构地区：[1]福建医科大学附属第一医院,福建省高血压研究所,福建福州350005

出　　处：《中华高血压杂志》2016年第2期141-146,共6页Chinese Journal of Hypertension

基　　金：福建医科大学临床医学重点学科(高血压学)项目资助(XK201107);福建医科大学女性课题(2012FN002);福建省教育厅立项课题(JB12106)

摘　　要：目的探讨早期氯沙坦干预对自发性高血压大鼠(SHR)成年后血压、心肌肥厚以及心肌中血管紧张素Ⅱ1型受体(AT1R)b亚型(AT1bR)和AT1R相关蛋白(ATRAP)基因启动子区甲基化的影响。方法将雄性SHR子鼠分为出生前、出生后、出生前后序贯氯沙坦干预组和非干预组。在8周龄和16周龄时,应用尾测法测定大鼠收缩压,称重并计算左心室质量(LVM)/体质量(BM),实时定量逆转录聚合酶链反应(RT-PCR)及Western-blot法测定左心室心肌AT1bR、ATRAP的mRNA及蛋白表达,重亚硫酸盐修饰PCR结合焦磷酸测序法测定AT1bR和ATRAP基因启动子区的甲基化水平。结果 16周龄时,3个氯沙坦干预组的SHR收缩压及LVM/BM较非干预组低[收缩压:出生前氯沙坦干预组(173.8±8.5),出生后氯沙坦干预组(145.4±9.7),出生前后序贯氯沙坦干预组(138.5±6.7)比非干预组(197.4±7.6)mm Hg;LVM/BM:出生前氯沙坦干预组(2.39±0.14),出生后氯沙坦干预组(2.00±0.11),出生前后序贯氯沙坦干预组(1.97±0.08)比非干预组(3.18±0.21)mg/g;均P<0.05]。与非干预组相比,3个氯沙坦干预组心肌中AT1bR mRNA和AT1R蛋白表达降低,ATRAP mRNA及蛋白表达升高,AT1bR基因启动子区的甲基化程度无改变,ATRAP基因启动子区的甲基化程度减少。结论早期氯沙坦干预能延缓SHR成年后血压的上升,改善心肌肥厚,减少心肌中ATRAP基因启动子区的甲基化。Objective To investigate the effect of early losartan treatment on blood pressure and cardiac hypertrophy in adult spontaneously hypertensive rats（SHR）,as well as the methylation in promoters of angiotensinⅡtype 1receptor（AT1R）subtype b（AT1b R）and AT1R-associated protein（ATRAP）genes in myocardium. Methods Male offspring of SHR were randomly assigned to four groups：prenatal losartan-treated group,postnatal losartantreated group,prenatal and postnatal sequential losartan-treated group and untreated group. Systolic blood pressure was measured by the tail-cuff method,and left ventricular mass/body mass（LVM/BM）was evaluated.mRNA and protein expression of AT1 bR and ATRAP,as well as the methylation of promoters of both genes in myocardium were determined by real-time reverse transcription-polymerase chain reaction（RT-PCR）,Western blot and bisulfite pyrosequencing,respectively.Results At 16 weeks of age,systolic blood pressure and LVM/BM in each group of losartan-treated rats were lower than those in untreated group [systolic blood pressure：prenatal losartantreated group（173.8±8.5）,postnatal losartan-treated group（145.4±9.7）,sequential losartan-treated group（138.5±6.7）vs untreated group（197.4±7.6）mm Hg;LVM/BM：prenatal losartan-treated group（2.39±0.14）,postnatal losartan-treated group（2.00±0.11）,sequential losartan-treated group（1.97±0.08）vs untreated group（3.18±0.21）mg/g;all P〈0.05]. The expressions of AT1 bR mRNA and AT1 R protein were downregulated,the expressions of ATRAP mRNA and protein upregulated in each group of losartan-treated rats compared with untreated group. Methylation percentage of ATRAP gene promoter was lower in each group of losartan-treated rats than untreated group,however,there was no difference in the methylation percentage of AT1 bR gene promoter among 4groups. Conclusion Early treatment with losartan may delay the increase of blood pressure,ameliorate cardiac hypertrophy later in adult SHR,and reduce methylation level of A

关 键 词：甲基化 血管紧张素Ⅱ1型受体 血管紧张素Ⅱ1型受体相关蛋白 自发性高血压大鼠 氯沙坦 基因 高血压 

分 类 号：R544.1[医药卫生—心血管疾病]