组蛋白脱乙酰酶2介导的组蛋白乙酰化失衡在压力过载性心肌重构中的作用  

Role of histone deacetylase 2-mediated histone acetylation imbalance in myocardial remodeling induced by pressure overload

作　　者：罗孝美 彭昌 吴书琪 张焕婷 田小春 LUO Xiao-mei;PENG Chang;WU Shu-qi;ZHANG Huan-ting;TIAN Xiao-chun(Department of Physiology,School of Basic Medical Sciences,Zunyi Medical University,Zunyi 563000,China;Depart-ment of Pediatrics,the Affiliated Hospital of Zunyi Medical University,Zunyi 563000,China)

机构地区：[1]遵义医科大学基础医学院生理教研室,贵州遵义563000 [2]遵义医科大学附属医院儿内科,贵州遵义563000

出　　处：《中国病理生理杂志》2022年第4期584-591,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金项目(No.82060046,No.81560040);遵义医科大学博士启动基金项目[院字(2015)4号];遵义医科大学大学生创新创业训练项目(No.ZYDC2018053)。

摘　　要：目的:探讨组蛋白脱乙酰酶2(histone deacetylase 2,HDAC2)介导的组蛋白乙酰化修饰失衡在压力过载性心肌重构中的调控作用。方法:选取SPF级成年昆明小鼠,通过部分结扎胸主动脉(transverse aortic con⁃striction,TAC)建立小鼠压力过载性心肌重构模型,应用表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)腹腔注射干预模型小鼠。根据随机数字表法将小鼠分为正常组、TAC组、溶剂组、假手术组和EGCG+TAC组,每组6只小鼠。收集各组小鼠心脏组织进行如下检测:Western blot检测HDAC2、第27位赖氨酸乙酰化的组蛋白H3(acetylated histone H3 at lysine 27,H3K27ac)、心肌细胞增强因子2A(myocyte enhancer factor 2A,MEF2A)和脑钠肽(brain natriuretic peptide,BNP)蛋白表达水平;超声心动图检测小鼠心功能;ES420生物系统检测小鼠左室收缩末期压力(left ventricular end-systolic pressure,LVESP)。结果:Western blot结果显示,TAC组小鼠心肌H3K27ac水平及心脏发育相关蛋白MEF2A和BNP表达水平较假手术组显著降低(P<0.05),而EGCG+TAC组小鼠心肌H3K27ac水平及MEF2A和BNP表达水平较TAC组显著升高(P<0.05)。HDAC2表达水平在TAC组较假手术组显著升高,而EGCG+TAC组HDAC2表达水平较TAC组显著降低(P<0.05);超声心动图及LVESP结果显示,TAC组小鼠心功能及LVESP较假手术组显著降低(P<0.05),而EGCG+TAC组小鼠心功能及LVESP与TAC组相比显著升高(P<0.05)。结论:EGCG能够抑制小鼠压力过载性心肌重构。HDAC2介导的H3K27乙酰化修饰可能是EGCG抑制压力过载性心肌重构的调控靶点之一。AIM:To investigate the regulatory role of histone acetylation modification imbalance mediated by histone deacetylase 2(HDAC2)in pressure overload-induced myocardial remodeling in mice.METHODS:The model of pressure overload-induced myocardial remodeling in specific pathogen-free adult Kunming mice was established by trans⁃verse aortic constriction(TAC).The model mice were intraperitoneally injected with epigallocatechin gallate(EGCG).According to random number table method,the mice were divided into normal group,sham group,vehicle group,TAC group and EGCG+TAC group,with 6 mice in each group.We then collected hearts from experimental mice after TAC for further analysis.The protein levels of HDAC2,acetylated histone H3 at lysine 27(H3K27ac),myocyte enhancer factor 2A(MEF2A)and brain natriuretic peptide(BNP)were assayed by Western blot.Cardiac function and left ventricular end-systolic pressure(LVESP)were examined by echocardiography and ES420 Biosystem,respectively.RESULTS:Western blot data showed that the acetylation level of H3K27 and the protein levels of MEF2A and BNP in TAC group were significantly lower than those in sham group(P<0.05),while those in EGCG+TAC group were significantly higher than those in TAC group(P<0.05).Meanwhile,the expression of HDAC2 in TAC group was significantly higher than that in sham group(P<0.05),while that in EGCG+TAC group was significantly lower than that in TAC group(P<0.05).The re⁃sults of echocardiography and LVESP showed that the cardiac function and LVESP of the mice in TAC group were signifi⁃cantly lower than those in sham group(P<0.05),while those in EGCG+TAC group were significantly higher than those in TAC group(P<0.05).CONCLUSION:Treatment with EGCG attenuates pressure overload-induced myocardial re⁃modeling in mice,and HDAC2-mediated H3K27 hypoacetylation may be one of the regulatory targets of EGCG.

关 键 词：组蛋白脱乙酰酶2 心肌重构 表没食子儿茶素没食子酸酯 

分 类 号：R542.2[医药卫生—心血管疾病] R363.2[医药卫生—内科学]