[ ABSTRACT] AIM: To investigate the regulatory mechanism of histone acetylation on cardiac hypertrophy in -duced by phenylephrine , and to provide a new idea for preventing and curing hypertrophic cardiomyopathy .METHODS:Phenylephrine was given by continuous subcutaneous injection for modeling cardiac hypertrophy in C 57BL/6 mice.The le-vel of histone H3 lysine 27 acetylation (H3K27ac) in the promoter of cardiac nuclear transcription factor GATA4 and the mRNA expression of GATA4 were identified by chromatin immunoprecipitation (ChIP) and real-time PCR, respectively. Meanwhile, the protein expression of histone H3K27ac, atrial natriuretic peptide (ANP) and α-myosin heavy chain (α-MHC) was determined by Western blot .Cardiac hypertrophy in the mice was observed by HE staining and echocardio-graphy.RESULTS:The results of Western blot showed that the level of histone H 3K27ac in phenylephrine group was sig-nificantly increased compared with normal saline group (P<0.05), and ChIP-qPCR data showed that the level of histone H3K27ac in the promoter of GATA4 was increased significantly in the same samples (P<0.05).The expression levels of GATA4 mRNA and ANP protein in phenylephrine group were apparently increased compared with normal saline group ( P<0.05).However, histone acetylase inhibitor anacardic acid attenuated histone H 3K27 hyperacetylation induced by pheny-lephrine, and downregulated the over-expression of GATA4 and ANP in the heart of the mice (P<0.05).HE staining and echocardiography data showed that phenylephrine apparently increased left ventricular posterior wall thickness and de -creased left ventricular end-systolic diameter and left ventricular end-diastolic diameter , while anacardic acid also reversed these indexes that mentioned above and attenuated cardiac hypertrophy induced by phenylephrine in the mice .CONCLU-SION:Histone acetylation modification imbalance is involved in cardiac hypertrophy induced by phenylephrine , and the histone acetylase inhibitor anacardic acid decreases histone hyperacetylation induced by phenylephrine and attenuates car -diac hypertrophy in the mice .%目的：探讨苯肾上腺素诱导小鼠心肌肥厚的组蛋白乙酰化调控机制，为防治肥厚性心肌病提供新的思路。方法：选取健康C57BL／6小鼠，苯肾上腺素皮下注射建立小鼠心肌肥厚模型，实时荧光定量聚合酶链反应（real-time PCR）和染色质免疫共沉淀技术（chromatin immunoprecipitation， ChIP）分别检测心脏核转录因子GATA结合蛋白4（GATA binding protein 4， GATA4） mRNA表达水平及其启动子区组蛋白H3第27位赖氨酸乙酰化（H3K27ac）水平，Western blot检测小鼠心肌组织组蛋白H3K27ac、心房钠尿肽（atrial natriuretic peptide， ANP）及α-肌球蛋白重链（α-myosin heavy chain ，α-MHC）的表达， HE染色及超声心动图观察小鼠心肌肥厚。结果： Western blot及ChIP-qPCR表明小鼠心肌组织组蛋白H3K27ac水平及GATA4启动子区组蛋白H3K27ac水平在苯肾上腺素组显著高于生理盐水对照组（P＜0.05），GATA4及ANP的表达水平在苯肾上腺素组也显著高于生理盐水对照组（P＜0.05）；而组蛋白乙酰化酶抑制剂漆树酸能够降低苯肾上腺素诱导的组蛋白H3K27的高乙酰化，且GATA4 mRNA及ANP蛋白的表达水平在漆树酸处理组也显著降低（ P＜0.05）；HE染色及超声心动图显示苯肾上腺素能够降低左室收缩末期内径（ left ventricular end-systolic diameter ， LVESD ）和左室舒张末期内径（ left ventricular end-diastolic diameter，LVEDD）并增加左室后壁（left ventricular posterior wall，LVPW）厚度，诱导小鼠心肌肥厚，而漆树酸能够提高LVESD和LVEDD并降低LVPW厚度，从而改善小鼠心肌肥厚。结论：组蛋白乙酰化修饰失衡参与了苯肾上腺素诱导的小鼠心肌肥厚，而组蛋白乙酰化酶抑制剂漆树酸能够下调苯肾上腺素诱导的组蛋白高乙酰化进而改善小鼠心肌肥厚。
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