EGCG升高cTnIR193H限制型心肌病模型小鼠未突变cTnI的表达水平

doi:10.12092/j.issn.1009-2501.2019.04.003

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (4): 376-382.doi: 10.12092/j.issn.1009-2501.2019.04.003

EGCG升高cTnIR193H限制型心肌病模型小鼠未突变cTnI的表达水平

张明清^1,2，刘玲娟²，田杰¹

¹重庆医科大学附属儿童医院，重庆400014； ²儿童发育疾病研究省部共建教育部重点实验室，重庆 400014

收稿日期:2018-07-22 修回日期:2019-01-09 出版日期:2019-04-26 发布日期:2019-05-01
通讯作者: 田杰，通信作者，男，博士，教授，主任医师，博士生导师，研究方向：小儿心血管疾病诊治，干细胞向心肌细胞分化机制、心脏发育与先天性心脏病的表观遗传机制研究。 Tel：13983003623 E-mail：100809@cqmu.edu.cn
作者简介:张明清，男，研究生，研究方向：心血管表观遗传学。 Tel：17391970355 E-mail：2281949425@qq.com
基金资助:
国家自然科学基金项目(81670212)

EGCG elevates wild-type cTnI expression in a cTnI-R193H mouse model of restrictive cardiomyopathy

ZHANG Mingqing^1,2，LIU Lingjuan ²，TIAN Jie ¹

¹ Children's Hospital of Chongqing Medical University，Chongqing 400014,China；²Key Laboratory of Developmental Disease in Childhood, Ministry of Education,Chongqing 400014,China

Received:2018-07-22 Revised:2019-01-09 Online:2019-04-26 Published:2019-05-01

摘要/Abstract

摘要：

目的:研究表没食子儿茶素没食子酸酯（EGCG）升高cTnIR193H限制型心肌病模型小鼠未突变cTnI的表达水平。方法:8周龄野生型C57小鼠及8周龄cTnIR193H限制型心肌病模型小鼠分别随机分为EGCG干预组、DMSO干预组以及未干预组。每周干预5 d，3个月后采集小鼠心脏组织。分别以Western blot与RT-PCR分别检测HDAC1、GATA4及cTnI 的mRNA表达水平。组蛋白H3K9乙酰化水平、cTnI基因启动子区域中的GATA4与HDAC1结合水平以ChIP-Q-PCR方式检测。结果:EGCG干预组未突变cTnI蛋白表达水平与mRNA表达水平、GATA4的mRNA表达水平、组蛋白H3K9乙酰化水平、cTnI启动子区域GATA4的结合水平均高于未干预组（P<0.05）。cTnI启动子区域HDAC1结合水平、HDAC1的mRNA表达水平均低于未干预组（P<0.05）。结论:在EGCG干预R193H模型小鼠实验中，EGCG可抑制HDAC1的表达，抑制cTnI启动子区域HDAC1的结合，促进心脏核心转录因子GATA4的表达、组蛋白H3K9的乙酰化、及cTnI启动子区域GATA4的结合，上调心肌的未突变cTnI的表达水平。

关键词: 表没食子儿茶素没食子酸酯, 心脏舒张功能障碍, 限制型心肌病, cTnI, 组蛋白乙酰化

Abstract:

AIM: To increase the expression level of normal cTnI in mice with cTnIR193H restricted cardiomyopathy by EGCG. METHODS: 8 weeks old wild type C57 mice and 8 weeks old cTnIR193H restricted cardiomyopathy model mice were randomly divided into EGCG intervention, DMSO intervention group and non intervention group. After 5 days of intervention, the heart tissues of mice were collected after 3 months. mRNA expression levels of HDAC1, GATA4 and cTnI were detected by Western blot and RT-PCR respectively. The acetylation level of histone H3K9, the binding level of GATA4 and HDAC1 in cTnI gene promoter region were detected by ChIP-Q-PCR. RESULTS:The level of protein level in the EGCG intervention group and the expression of normal cTnI at the level of mRNA, the level of mRNA expression of GATA4, the level of histone H3K9 acetylation, and the binding level of GATA4 were higher than those of the unpretreated group (P<0.05). The level of HDAC1 binding and HDAC1 mRNA expression level in cTnI promoter region were lower than those in the non intervention group (P<0.05). CONCLUSION: In the R193H model mice, EGCG inhibits the expression of HDAC1 and inhibits the binding of HDAC1 in the promoter region of cTnI, thus promoting the expression of cardiac transcription factor GATA4, the acetylation of histone H3K9, and the combination of GATA4 in the promoter region of cTnI, and up regulation of the cTnI expression of myocardium.

Key words: (-)-epigallo-catechin-3-gallate, cardiac diastolic dysfunction, restrictive cardiomyopathy, cTnI, histone acetylation

中图分类号:

R965.2

张明清，刘玲娟，田杰. EGCG升高cTnIR193H限制型心肌病模型小鼠未突变cTnI的表达水平[J]. 中国临床药理学与治疗学, 2019, 24(4): 376-382.

ZHANG Mingqing，LIU Lingjuan，TIAN Jie. EGCG elevates wild-type cTnI expression in a cTnI-R193H mouse model of restrictive cardiomyopathy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(4): 376-382.

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EGCG升高cTnIR193H限制型心肌病模型小鼠未突变cTnI的表达水平

EGCG elevates wild-type cTnI expression in a cTnI-R193H mouse model of restrictive cardiomyopathy

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