组蛋白乙酰化修饰失衡在苯肾上腺素诱导小鼠心肌肥厚中的调控作用

发布时间：2018-07-07 10:06

本文选题：苯肾上腺素 + 心肌肥厚　；参考：《中国病理生理杂志》2017年02期

【摘要】：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(P0.05),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(P0.05);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GATA4mRNA及ANP蛋白的表达水平在漆树酸处理组也显著降低(P0.05);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 enddiastolic 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。
[Abstract]:Aim: to explore the mechanism of histone acetylation in myocardial hypertrophy induced by phenylephrine in mice, and to provide a new idea for prevention and treatment of hypertrophic cardiomyopathy. Methods: myocardial hypertrophy model was established by subcutaneous injection of phenylephrine in healthy C57BL / 6 mice. Real-time fluorescence quantitative polymerase chain reaction (real-time PCR) and chromatin immunoprecipitation assay (chip) were used to detect the expression of GATA-binding protein 4 (GATA4) mRNA and lysine acetylation at the 27th position of the promoter H3, respectively. The expression of histone H3K27ac, atrial natriuretic peptide (atrial natriuretic peptideANP, 伪 -myosin heavy chain (伪 -MHC) and myocardial hypertrophy in mice were detected by HE staining and echocardiography. Results Western blot and ChIP-qPCR showed that the levels of histone H3K27ac in myocardial tissue and histone H3K27ac in GATA4 promoter were significantly higher in phenylephrine group than in saline control group (P0.05). The expression levels of histone H3K27ac and GATA4 promoter in phenylephrine group were also significantly higher than those in phenylephrine group (P0.05). In the saline control group (P0.05), the histone acetylase inhibitor, lacquer acid, decreased the hyperacetylation of histone H3K27 induced by phenylephrine. The expression level of GATA4 mRNA and ANP protein was also significantly decreased in the lacquer acid treatment group (P0.05). The results of HE staining and echocardiography showed that phenylephrine could decrease the left ventricular end-systolic diameter (left ventricular end-systolic diameterus LVESD) and the left ventricular end-diastolic diameter (left ventricular enddiastolic diameterus LVEDD). The thickness of left ventricular posterior wall (left ventricular posterior wall PW), Myocardial hypertrophy was induced in mice, while lveSD and LVEDD were increased and LVPW thickness was decreased, which resulted in the improvement of myocardial hypertrophy in mice. Conclusion: the imbalance of histone acetylation is involved in myocardial hypertrophy induced by phenylephrine, while histone acetylase inhibitor laccaric acid can down-regulate histone hyperacetylation induced by phenylephrine and improve myocardial hypertrophy in mice.
【作者单位】：遵义医学院附属医院儿内科;遵义医学院基础医学院生理教研室;重庆医科大学附属儿童医院心内科;
【基金】：国家自然科学基金资助项目(No.81560040) 遵义医学院博士启动基金资助项目(院字(2015)4号) 遵义医学院与科技学院大学生创新训练项目(遵医科院【2015】3108号)
【分类号】：R542.2

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