中文摘要：

目的探讨表没食子儿茶素没食子酸酯[（-）-epigallo-catechin-3-gallate，EGCG]能否通过抑制组蛋白去乙酰化酶1（histone deacetylase1，HDACl）参与老年小鼠心脏SERCA2a的表达。方法24只16月龄雄性C57BL／6老年小鼠随机数字表法分为EGCG＋老年组[腹腔注射50mg／（kg·d）的EGCG]、DMSO＋老年组（腹腔注射与溶解EGCG同剂量的二甲基亚砜）以及未处理老年组，每组8只；3月龄雄性C57BL／6成年小鼠作为青年组（n=8）。干预8周，收集心脏组织。RT-PCR检测Atp2a2及HDACl的mRNA表达量，Westernblot检测SERCA2a的表达量。ChIP-Q-PCR检测Atp2a2启动子区组蛋白AcH3K9水平及HDACl、GATA4、Mef2c的结合量。结果RT-PCR及Western blot结果表明，老年小鼠心脏SERCA2a在mRNA及蛋白水平的表达降低（P〈0．05），HDACl在mRNA水平表达升高（P〈0．05）。ChIP-Q-PCR结果表明，老年小鼠心脏Atp2a2启动子区HDACl结合量升高，组蛋白AcH3K9水平降低，GATA4、Mef2c的结合量降低（P〈0．05）。EGCG干预8周后，老年小鼠心脏HDACl的表达量及其在Atp2a2启动子区的结合量降低，组蛋白AcH3K9水平升高，GATA4、Mef2c的结合量增加（P〈0．05），EGCG在mRNA及蛋白水平升高了老年小鼠心脏SERCA2a的表达（P〈0．05）。结论由HDACl介导的组蛋白H3K9低乙酰化可能是老年小鼠心脏SERCA2a表达降低的关键机制之一，EGCG通过抑制这一过程升高老年小鼠心脏SERCA2a的表达。

英文摘要：

Objective To investigate whether （ - ） -epigallo-catechin-3-gallate （ EGCG ） could regulate the expression of sarcoplasmic reticulum Ca^2＋ ATPase （SERCA2a） by inhibiting histone deacetylase 1 （ HDAC1 ） in aging mice hearts. Methods A total of 24 16-month-old C57 BL/6 male aging mice were randomly divided into EGCG group [50 mg/（kg · d） EGCG], DMSO group and untreated old group （n =8 for each group）, and another 8 3-month-old male mice were assigned as young group. The mice from the EGCG group and DMSO group were treated with EGCG and DMSO by intraperitoneal injection for 8 weeks, respectively. Then all the mice were sacrificed and the heart tissues were harvested from each group. RT-PCR was used to measure the mRNA expression level of Atp2a2 and HDAC1. Meanwhile, the protein level of SERCA2a was detected by Western blotting. The binding levels of HDAC1, acetylated lysine 9 on histone H3 （AcH3K9） and transcription factors GATA4 and Mef2c near the proximal promoter region of Atp2a2 gene were determined by ChIP-Q-PCR. Results The results of RT-PCR and Western blotting showed a signifieant decrease of SERCA2a in the aging hearts at both mRNA and protein levels （P 〈 0.05 ）, but the expression of HDAC1 was increased at mRNA level in aging hearts （P 〈 0.05 ）. ChIP-Q-PCR demonstrated that the amount of HDAC1 binding to proximal promoter region of Atp2a2 gene was significantly increased, but the binding levels of AcH3Kg, GATA4 and Mef2c were reduced in aging hearts （P 〈0.05）. After intervention by EGCG for 8 weeks, there were decreases in the expression and binding amount of HDAC1, and rises in AcH3K9, GATA4 and Mef2c binding levels near the proximal promoter region of Atp2a2 gene in aging hearts. EGCG also increased the expression of Atp2a2 gene at both mRNA and protein levels in aging hearts （ P 〈 0.05 ）. Conclusion Hypoacetylation of AcH3K9 mediated by HDAC1 may play a critical role in low expression of SERCA2a in aging hearts, and EGCG could inhibit the process an