三参通脉合剂对慢性心力衰竭microRNA-146-TLR-4-NF-κB信号通路的调控干预研究

The latest researches showed that Chronic heart failure is closely related with inflammatory reaction. MicroRNA-146 is believed to be involved in TLR-4-NF-κB signaling pathway in the immune system and it may play an important role in the pathological process of chronic heart failure for reduceing inflammatory reaction. Meanwhile, the previous research of SSTM has found that the SSTM may reduce inflammation reaction in coronary heart disease. Also, chronic heart failure is the end stage of progression of coronary artery disease, it can be inferred that microRNA-146-TLR-4-NF-κB pathway may be an play an important role of it. This study establish animal models of chronic heart failure, study on the mechanism of microRNA-146 regulated-TLR-4-NF-κB pathway by SSTM intervention in inflammatory reaction and try to provide a new and effective target and prescriptions for the treatment of chronic heart failure.

新近研究表明炎症反应所致心肌损伤与慢性心力衰竭密切相关，microRNA-146被认为在慢性心力衰竭中主要通过负反馈环路调控下游TLR-4-NF-κB信号通路（IRAK1和TRAF6）从而介导慢性炎症反应减轻心肌损伤。另外，对三参通脉合剂的早期研究发现该药物参与了冠心病免疫效应的诱导和调节，纠正了患者免疫功能的紊乱。慢性心力衰竭是冠心病进展的终末阶段，目前临床慢性心力衰竭患者多源于长年冠心病进行性发展或急性心肌梗死后缺血再灌注。因此我们推测炎症相关microRNA-146-TLR-4-NF-κB通路可能是抗心肌损伤，治疗慢性心力衰竭的重要靶点。本研究以炎症反应引起心肌损伤为基础，拟建立慢性心力衰竭动物模型，研究三参通脉合剂对microRNA-146-TLR-4-NF-κB信号通路的干预机制，并在后期进行离体细胞实验加以验证，为治疗慢性心力衰竭提供新的思路。

本研究通过模拟慢性心力衰竭动物及细胞模型，从体内、体外两个维度，探讨了三参通脉合剂治疗慢性心力衰竭的分子学机制，发现microRNA-146可以通过负反馈环路调控下游TLR-4-NF-κB信号通路(IRAK1和TRAF6)从而介导慢性炎症反应减轻心肌损伤。由此推测炎症相关microRNA-146-TLR-4-NF-κB通路可能是抗心肌损伤，治疗慢性心力衰竭的重要靶点。