作者：姬婧，张海召，朱祥彬，陈泽娥，欧阳昆富，贺松，张佳纯，高燕

单位：

1.518034广东省深圳市，北京大学深圳医院心血管外科　2.518101广东省深圳市前海蛇口自贸区医院心血管内科　3.518101广东省深圳市前海蛇口自贸区医院医学检验科

Units：

1.Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen 518034, China2.Department of Cardiovascular Medicine, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen 518101, China3.Department of Medical Laboratory, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen 518101, China

关键词：

心肌疾病；肌细胞，心脏；大鼠；MC1568；胎牛血清；组蛋白去乙酰化酶

Keywords：

Cardiomyopathies; Myocytes, cardiac; Rats; MC1568; Fetal bovine serum; Histone deacetylase

CLC：

R 542.2

DOI：

10.12114/j.issn.1008-5971.2023.00.283

Funds：

国家自然科学基金青年科学基金项目（ 82200450 ）；深圳市科技创新委员会科技计划项目（JCYJ20180301170636978）；深圳市南山区引进高层次医学团队立项项目（202103016）

摘要：

目的　探讨MC1568对胎牛血清（FBS）诱导的大鼠乳鼠心肌细胞肥大的作用及其机制。方法　本实验时间为2021年5月至2022年11月。选取出生3 d内的SPF级SD大鼠乳鼠40只，分离并培养其心肌细胞。取原代大鼠乳鼠心肌细胞，将其随机分为对照组（不进行干预）、FBS组（加入20% FBS培养48 h以诱导心肌细胞肥大）、曲古抑菌素A（TSA）组（加入20% FBS及200 nmol/L TSA培养48 h）、MC1568组（加入20% FBS及10 μmol/L MC1568培养48 h）。采用α-辅肌动蛋白染色检测各组心肌细胞表面积，采用RT-qPCR法检测各组心肌肥大标志物〔心房利钠肽（ANP）、β-肌球蛋白重链（MHC）〕mRNA表达水平，采用Western blot检测各组心肌细胞中P300、组蛋白去乙酰化酶（HDAC）4、磷酸化HDAC4（pHDAC4）表达水平。结果　FBS组心肌细胞表面积大于对照组、TSA组、MC1568组（P＜0.05）。FBS组ANP、β-MHC mRNA表达水平高于对照组、TSA组、MC1568组（P＜0.05）。四组心肌细胞中HDAC4表达水平比较，差异无统计学意义（P＞0.05）；FBS组心肌细胞中P300表达水平高于对照组、TSA组，pHDAC4表达水平高于对照组、TSA组、MC1568组（P＜0.05）。结论　FBS可引起心肌细胞肥大，而MC1568可以抑制心肌细胞肥大，其保护作用可能与抑制HDAC4/MEF2D信号通路有关。

Abstract：

Objective To investigate the effect and mechanism of MC1568 on cardiomyocyte hypertrophy inducedby fetal bovine serum (FBS) in neonatal rats. Methods This experiment was conducted form May 2021 to November 2022.Forty SPF grade SD neonatal rats born within 3 days were selected, and their myocardial cells were isolated and cultured. Primaryneonatal rat cardiomyocytes were randomly divided into control group (without intervention) , FBS group (cultured with 20% FBSfor 48 h to induce cardiomyocyte hypertrophy) , trichostatin A (TSA) group (cultured with 20% FBS and 200 nmol/L TSA for 48 h)and MC1568 group (cultured with 20% FBS and 10 μmol/L MC1568 for 48 h) . The surface area of cardiomyocytes in each groupwas detected by α-coactin staining. The mRNA expression levels of myocardial hypertrophy markers [atrial natriuretic peptide(ANP) ,β-myosin heavy chain (MHC) ] in each group were detected by RT-qPCR. Western blot was used to detect the expressionlevels of P300, histone deacetylase (HDAC) 4 and phosphorylated HDAC4 (pHDAC4) in cardiomyocytes of each group. ResultsThe surface area of cardiomyocytes in FBS group was larger than that in control group, TSA group and MC1568 group (P <0.05) . The mRNA expression levels of ANP and β-MHC in FBS group were higher than those in control group, TSA group andMC1568 group (P < 0.05) . There was no significant difference in HDAC4 expression level among the four groups (P > 0.05) . Theexpression level of P300 in cardiomyocytes of FBS group was higher than that of control group and TSA group, and the expressionlevel of pHDAC4 was higher than that of control group, TSA group and MC1568 group (P < 0.05) . Conclusion FBS can causecardiomyocyte hypertrophy, while MC1568 can inhibit cardiomyocyte hypertrophy, and its protective effect may be related to the inhibition of HDAC4/MEF2D signaling pathway.

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