MLL4介导的组蛋白甲基化修饰在针刺改善糖尿病心肌病小鼠异常脂代谢中的作用研究

研究证实针灸在调节糖尿病脂代谢异常，治疗和延缓DCM进展方面确有疗效，但机制研究匮乏。越来越多证据显示组蛋白甲基化修饰与糖尿病心肌病的发生发展密切相关，尤其与引起该病理过程的主要病理因素——脂代谢异常关系密切。基于本课题组在针刺降脂和治疗心脏疾病表观遗传学机理上的研究成果，紧密跟踪前沿理论与技术，提出了“电针能通过调控组蛋白甲基化水平来改善异常的脂代谢，从而延缓糖尿病心肌病的病理进程，并运用心脏特异性敲除Mll4小鼠对此进行验证”的假说。围绕这一假说，拟通过运用心肌特异性敲除组蛋白甲基转移酶MLL4小鼠的糖尿病心肌病模型，采用生理学、病理学、分子生物学等技术，证实MLL4介导的组蛋白甲基化修饰在针刺改善糖尿病心肌病小鼠异常脂代谢中的关键作用，并从表观遗传学调控的角度深入揭示其机制，以期为针灸改善糖尿病心肌病的症状在临床的应用及推广提供可靠的科学证据。

Lots of studies have confirmed the efficacy of acupuncture in regulating abnormal diabetic lipid metabolism, treating and delaying the progression of diabetic cardiomyopathy (DCM), but the mechanism is very scarce. More and more evidence show that histone methylation is closely related to the occurrence and development of DCM, especially the abnormal lipid metabolism, which is the main pathogenesis during this process. Based on our previous research progress in regulating lipid and treatment of heart disease by acupuncture from epigenetic aspect, we closely track the frontier theory and technique, then propose that "Electroacupuncture can improve abnormal lipid metabolism by regulating the level of histone methylation, thus delay the pathological process of diabetic cardiomyopathy, and verify this by using Mll4 cardio-specific knockout mice ". To examine this hypothesis, we use myocardial specific knockout histone methyltransferase MLL4 model for DCM, then apply many technologies, such as physiology, pathology, molecular biology to employ its mechanism. The role of MLL4-mediated histone methylation in improving abnormal lipid metabolism by acupuncture in DCM will be investigated and further mechanism from epigenetic regulation aspect will also be determined in this study, so as to provide reliable scientific evidence for acupuncture to improve the symptom of diabetic cardiomyopathy in clinical application.