辛二酰苯胺异羟肟酸通过抑制组蛋白去乙酰化酶改善小鼠心肌肥厚的研究

发布时间：2018-04-24 10:10

本文选题：组蛋白去乙酰化酶 + 心脏扩大　；参考：《中国循环杂志》2017年08期

【摘要】：目的:探讨组蛋白去乙酰化酶(HDAC)抑制剂辛二酰苯胺异羟肟酸(SAHA)改善小鼠心肌肥厚的作用,为防治心肌肥厚提供新思路。方法:选取60只昆明小鼠,随机分为正常组、假手术组、心肌肥厚组、心肌肥厚+SAHA组,通过部分结扎小鼠胸主动脉建立心肌肥厚模型,最终每组纳入6只。采用苏木素伊红(HE)染色观察小鼠心肌细胞,超声心动图检测小鼠心功能,比色法检测HDAC活性,小鼠心肌组织中HDAC亚型HDAC5和β-肌球蛋白重链(β-MHC)信使核糖核酸(mRNA)和蛋白表达水平分别运用逆转录-聚合酶链反应(RT-PCR)和蛋白免疫印迹(Western blot)检测。结果:HE染色结果表明心肌肥厚组小鼠心肌细胞肥大、排列紊乱、细胞核深染。心肌肥厚组小鼠左心室舒张末期直径、左心室舒张末期容积均显著低于假手术组(P0.05),而室间隔明显较假手术组增厚(P0.05)。心肌肥厚组小鼠HDACs活性显著高于假手术组(P0.05);心肌肥厚组HDAC5和β-MHC的mRNA及蛋白表达水平均显著高于假手术组(P0.05)。SAHA能够显著降低HDAC5表达水平,显著下调心脏肥厚相关基因β-MHC的表达并改善小鼠心功能和心肌肥厚(P均0.05)。结论:HDAC参与了心肌肥厚的发生,HDAC抑制剂SAHA通过抑制HDAC5的表达从而改善小鼠心肌肥厚。
[Abstract]:Aim: to investigate the effect of histone deacetylase (HDAC) inhibitor, octylaniline hydroxamic acid (SAHAA), on myocardial hypertrophy in mice, and to provide a new idea for prevention and treatment of myocardial hypertrophy. Methods: sixty Kunming mice were randomly divided into normal group, sham operation group, myocardial hypertrophy group and myocardial hypertrophy SAHA group. Myocardial hypertrophy model was established by partial ligation of thoracic aorta of mice. The cardiac myocytes of mice were observed by hematoxylin eosin (HEH) staining, the cardiac function of mice was detected by echocardiography, and the activity of HDAC was detected by colorimetric method. The expression of HDAC subtype HDAC5 and 尾 -myosin heavy chain (尾 -MHCM) mRNA mRNA and protein were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting (Western blot), respectively. Results the results showed that the cardiac myocytes in the hypertrophic group were hypertrophic, disordered, and the nuclei were deeply stained. The left ventricular end-diastolic diameter and left ventricular end-diastolic volume in the hypertrophic group were significantly lower than those in the sham operation group (P 0.05), while the ventricular septum was significantly thicker than that in the sham operation group. The expression of mRNA and protein in HDAC5 and 尾 -MHC in myocardial hypertrophy group was significantly higher than that in sham operation group, and the expression level of mRNA and protein in HDAC5 and 尾 -MHC in myocardial hypertrophy group was significantly higher than that in sham operation group. The expression of cardiac hypertrophy related gene 尾 -MHC was significantly down-regulated and the cardiac function and cardiac hypertrophy were significantly improved in mice. Conclusion SAHA is involved in the pathogenesis of myocardial hypertrophy and can improve myocardial hypertrophy by inhibiting the expression of HDAC5 in mice.
【作者单位】：遵义医学院附属医院儿内科;遵义医学院生理教研室;
【基金】：国家自然科学基金项目(81560040) 遵义医学院博士启动基金项目[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]
【分类号】：R542.2

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