苗药大果木姜子油CV-3介导miR-328调控心房颤动的分子机制研究

心房颤动(AF) 是临床常见和严重的心律失常，新进研究表明AF与miR-328异常调节密切相关。本课题组前期研究发现房颤时miR-328的下游因子LTCCα1c亚单位mRNA蛋白表达明显下降；同时发现苗药大果木姜子油(CV-3)具有防治房颤作用，其具体药效机制是否通过miR-328实现有待深入研究。基于此，本项目拟在细胞和动物水平验证miR-328 、Ca2+、CaM、Cav1.2的表达变化；探索miR-328与心房颤动时心肌细胞增殖、凋亡和细胞超微结构改变的相关性；同时通过干扰和过表达miR-328体系的制备明确其关键蛋白身份；验证CV-3是否通过调控miR-328的表达改善AF发生，为AF治疗的新分子药物靶标提供重要线索；解析CV-3通过抗氧化、抗炎和抗凋亡的综合治疗心房颤动作用，为苗药CV-3临床应用提供客观依据。

Atrial fibrillation(AF) is the most common clinical arrhythmia, new research suggests that AF is closely related to the abnormal miR - 328 regulation.In our previous study, we found that the expression of LTCC subunit mRNA and protein in the downstream of the miR-328 decreased significantly, so we hope to further analyze the molecular mechanism of miR-328 in the regulation of AF in AF.At the same time, our study indicated that CV-3 is beneficial for AF, whether the efficacy mechanism is realized by miR-328 is worth exploring.Therefore, our project is going to show the expression of cell and animal level verification of miR-328, Ca2+, CaM, Cav1.2,to explore the relationship between miR-328 and myocardial cell proliferation, apoptosis and ultrastructural changes in AF,and to through the interference and overexpression of miR - 328 system of the preparation to clear the key protein identification;In addition, to verify whether CV-3 can improve the occurrence of AF by regulating the expression of miR-328, and provide important clues for the new molecular drug targets of AF therapy;Objective to analyze the effect of CV-3 on the treatment of AF by anti oxidant, anti-inflammatory and anti apoptosis, and provide the objective basis for the clinical treatment of AF with CV-3.