染色质重塑对房颤心房肌肥大基因转录调控影响的研究

项目名称： 染色质重塑对房颤心房肌肥大基因转录调控影响的研究

项目编号： No.81500258

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 郑柳颖

作者单位： 天津市第五中心医院

项目金额： 18万元

中文摘要： 心房颤动是导致循环栓塞和脑血管意外的最常见、最重要原因之一，有极高的致残率和致死率。房颤的治疗一直未获突破性进展，归其原因主要在于对房颤发病机制仍然认识不够深入，启动、维持房颤的关键因素不清楚。因此，研究房颤的发病基础、对其进行干预，寻找根本的防治方法已成为当前房颤治疗研究的热点。本课题拟通过检测房颤病人：心房肌细胞表面积、肥大基因蛋白表达和染色质组蛋白乙酰化水平，证实房颤时存在心房肌细胞肥大、肥大基因再表达和染色质组蛋白乙酰化修饰；利用AngII体外诱导心房肌细胞，构建肥大细胞模型，检测心房肌肥大基因：染色质结构松散度、染色质组蛋白特定赖氨酸位点乙酰化修饰、募集转录因子能力等的变化，证实肥大刺激能够通过诱导肥大基因启动子序列染色质重塑，促进转录因子与启动子结合，启动肥大基因转录，促进房颤的进程。此课题是在表观遗传学领域对房颤发病机制的新探索，能够为临床治疗房颤动提供新的干预靶点。

中文关键词： 心房颤动；肥大基因；染色质重塑；转录调控；组蛋白修饰

英文摘要： Atrial fibrillation is one of the important causes leading to circulation embolism and cerebrovascular accident with high morbidity and mortality. After cardioversion of atrial fibrillation within one year，recurrence rate is still high. therefore, to study the onset and basis of atrial fibrillation, to find the fundamental method of prevention and cure has become the current hot topics in the study of treatment of atrial fibrillation. This topic proposed by examining patients with atrial fibrillation: surface area of atrial myocyte, protein expression and chromatin histone acetylation level of hypertrophy gene. Confirmed the existence of hypertrophy in atrial myocyte、expression of hypertrophic gene and acetylation modification in chromatin histone; Incubation atrial myocyte in vitro using AngII ，hypertrophic myocyte model was constructed.By detecting the friability of chromatin structure、the ability of raising acetylation of histone acetyltransferase and enzyme、acetylated modification of chromatin histone lysine、the ability of raising transcription factor，confirm that hypertrophic stimulus can promote acetylated modification of specific lysine loci in hypertrophy genome, induce chromatin remodeling of hypertrophy gene：tend to be loose and open, thus increase the combination of transcription factors with promoter sequences, activate the transcription of hypertrophy gene, promote the process of atrial fibrillation.The research is a new exploration for pathogenesis of atrial fibrillation in the field of epigenetics. It provides new targets for intervention of atrial fibrillation in clinical treatment.

英文关键词： atrial fibrillation;hypertrophic gene;chromatin remodeling;transcriptional regulation;histone modification