肝心和合法调控microRNAs及其靶基因表达稳定AS易损斑块作用机制研究

“Liver-and-Heart”Theories Regulate MicroRNAs and Target Gene Expression Stable Atherosclerosis Vulnerable Plaques

心血管疾病是我国目前高发病率、高致残率、高死亡率的疾病之一,动脉粥样硬化(AS)是心血管病的病理基础。肝失疏泄膏脂转输障碍是血脂异常关键病机,而血脂异常是AS重要危险因素。如何有效的延缓AS的进展,对心血管病的防治具有重要意义。随着中医现代化的不断深入,中医药在AS的防治过程中发挥着越来越重要的作用,尤其在疏肝理气通脉方面已显示出较高的有效性和安全性。清脂通脉颗粒作为“疏肝清脂”治法的代表方,以其疏肝清脂通脉之功而被应用于AS的防治中。前期研究团队研究发现了清脂通脉颗粒多靶点-多通路抗AS的作用特点,本课题通过高脂喂饲ApoE基因敲除小鼠建立AS小鼠模型,并给予清脂通脉颗粒干预,观察小鼠血脂水平、动脉脂质含量及斑块形态的改变,探讨清脂通脉颗粒调控miR-33、miR-122对其下游通路ABCA1、ABCG1及NPC1抗AS的机制,并通过体外实验加以验证,为防治AS的中医药研究提供实验依据。

Cardiovascular disease is one of the diseases with high morbidity,disability and mortality in China.Atherosclerosis(AS)is the pathological basis of cardiovascular disease.Impaired lipid transfer in liver diarrhea and cream is the key pathogenesis of dyslipidemia,and dyslipidemia is an important risk factor for AS.How to effectively delay the progress of AS is of great significance for the prevention and treatment of cardiovascular disease.With the continuous deepening of the modernization,traditional Chinese medicine has played an increasingly important role in the prevention and treatment of AS,and has shown a high degree of effectiveness and safety,especially in the treatment of soothing liver Qi and dredging meridians.Qingzhi Tongmai Granule(清脂通脉颗粒),as the representative of soothing liver Qi and clearing lipids method,has been used in the prevention and treatment of AS due to its function of relieving liver and clearing fat.The previous research group found the anti-AS characteristics of Qingzhi Tongmai Granule with multiple targets and multiple pathways.In this project,a mouse model of AS was established by feeding high-fat ApoE knockout mice and Qingzhi Tongmai Granules were given intervention to observe the changes of blood lipid level,arterial lipid content and plaque morphology in mice,and explore the mechanism of Qingzhi Tongmai Granules regulating miR-33 and miR-122 on their downstream pathways ABCA1,ABCG1 and NPC1 against AS,and in vitro experiments it is verified to provide experimental basis for the research of traditional Chinese medicine for the prevention and treatment of AS.