心肌细胞肥大过程中心脏发育相关转录因子及下游心脏肥大标志基因的时序性表达规律研究

发布时间：2018-04-28 12:21

本文选题：心肌细胞肥大 + 心脏发育相关转录因子　；参考：《解放军医学杂志》2017年05期

【摘要】：目的观察在心肌细胞肥大过程中心脏发育相关转录因子及下游心脏肥大标志基因时序性表达规律,为心肌肥大机制研究提供线索。方法用异丙肾上腺素(ISO)干预心肌细胞,用CCK-8、细胞计数仪、免疫组化分别检测细胞存活率、细胞直径及表面积,用RT-PCR、Western blotting分别检测相关基因mRNA及蛋白表达水平。结果用ISO成功构建心肌细胞肥大模型。ISO干预后,GATA结合蛋白4(GATA4)、肌细胞增强因子2C(MEF2C)、GATA5、脑钠肽(BNP)、心房利钠因子(ANP)于24h开始升高,P300、α-肌球蛋白重链(α-MHC)、T-框蛋白5(TBX5)于12h开始升高,血清应答因子(SRF)、β-MHC mRNA于6h开始升高(P0.05);其中GATA4、α-MHC、β-MHC、SRF、P300 mRNA表达呈先升后降的趋势,至干预72h GATA4、SRF、α-MHC、β-MHC、P300 mRNA表达仍高于正常(P0.05),而MEF2C降至正常(P0.05);GATA5、TBX5、ANP、BNP mRNA表达与对照组相比持续升高(P0.05),而NKX2.5 mRNA(P0.05)无明显变化。ISO干预48h后,GATA4蛋白表达水平升高,HEY2蛋白表达水平降低(P0.05)。结论在心肌细胞肥大过程中,MEF2C的时序表达规律与心脏发育过程相似,而GATA4、GATA5、SRF、TBX5的时序性表达规律与心脏发育过程不完全一致,提示其在心肌细胞肥大由代偿转为失代偿过程中的重要作用。同时GATA4、MEF2C、SRF与乙酰化酶P300的时序性表达规律相似,提示在心肌细胞肥大过程中其时序性表达可能受P300调控。
[Abstract]:Objective to observe the temporal expression of transcription factors associated with cardiac development and downstream markers of cardiac hypertrophy during cardiomyocyte hypertrophy so as to provide clues for the study of cardiac hypertrophy mechanism. Methods Cardiac myocytes were treated with isoproterenol (ISO). The cell survival rate, cell diameter and surface area were detected by CCK-8, cell counter and immunohistochemistry, and the expression of mRNA and protein were detected by RT-PCR- Western blotting. Results the model of cardiomyocyte hypertrophy was successfully constructed with ISO. After the intervention of ISO, GATA4, GATA5, brain natriuretic peptide and atrial natriuretic factor began to increase at 24 h, and 伪 -MHCT- THC THC 5 TBX5 began to increase at 12 h. The expression of 尾 -MHC mRNA began to increase at 6 h, and the expression of GATA4, 伪 -MHC, 尾 -MHC1 SRFFP300 mRNA increased first and then decreased. At 72 h after intervention, the expression of GATA4, 伪 -MHC, 尾 -MHCP300 mRNA was still higher than that of normal P0.05, while the expression of MEF2C decreased to P0.05TBX5ANPNP-BNP mRNA, but NKX2.5 mRNAP0.05) had no significant change. Conclusion the temporal expression of MEF2C in cardiomyocyte hypertrophy is similar to that in cardiac development, but the temporal expression of GATA4, GATA5, SRF5, TBX5 is not completely consistent with that of cardiac development. The results suggest that it plays an important role in the process of cardiomyocyte hypertrophy from compensation to decompensation. At the same time, the sequential expression of GATA4MEF2CfSRF was similar to that of acetylase P300, suggesting that its timing expression might be regulated by P300 in the process of cardiomyocyte hypertrophy.
【作者单位】：重庆医科大学附属儿童医院心血管内科与小儿心血管病研究室、儿童发育疾病研究省部共建教育部重点实验室、重庆市儿童发育重大疾病诊治与预防国际科技合作基地、儿科学重庆市重点实验室;
【基金】：国家自然科学基金(81270234,81570218) 重庆市社会民生科技创新专项项目(cstc2015shmszx120043)~~
【分类号】：R542.2

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