慢性心力衰竭（chronic heart failure,CHF）与线粒体融合-分裂失衡密切相关。长链OPA1(L-OPA1)是线粒体融合的必需要素，而短链OPA1（S-OPA1）蓄积则促进线粒体裂解。近期研究发现心肌YME1L敲除后激活OMA1，OMA1切割L-OPA1，使L-OPA1过度向S-OPA1转化，导致线粒体融合-分裂失衡而发生线粒体碎片化并导致CHF，提示调控OMA1/OPA1可成为治疗CHF的有效途径。强心汤功能益气温阳、活血利水，对CHF有较好疗效。本课题拟复制大鼠心梗后CHF模型和缩窄腹主动脉CHF模型，观察OMA1活化情况，明确OMA1/OPA1介导的线粒体碎片化在两种模型中的作用，采用体内转染技术观察分别封闭YME1L、OMA1及同时封闭两者对线粒体形态、心肌代谢、心功能的影响，探讨有效治疗靶点，并观察强心汤的干预影响，为益气温阳、活血利水法防治CHF提供科学依据。

Imbalanced fusion and fission of mitochondria and chronic heart failure (CHF)are intimately linked. Proteolytic processing of the dynamin-like guanosine triphosphatase (GTPase) OPA1 in the inner membrane of mitochondria is emerging as a critical regulatory step to balance mitochondrial fusion and fission. from long (L-OPA1) is required for mitochondrial fusion, but S-OPA1 is not, although accumulation of short forms (S-OPA1) in excess accelerates fission. A recently study found that Cardiac-specific ablation of Yme1l in mice activated the mitochondrial proteases OMA1which cleave OPA1 from L-OPA1 to S-OPA1 and triggered mitochondrial fragmentation and altered cardiac metabolism.This caused CHF and identified OMA1 as a critical regulator of mitochondrial morphology and cardiac function and OMA1/OPA1 could be a therapeutic target for CHF.Qiangxin Decoction is effective for CHF. This study, we will build up the rat model of CHF after myocardial infarction and the abdominal aorta coarctation CHF model to imitate the process of CHF caused by coronary heart disease and hypertension. We will Observe the activation of OPA1 and the Yme1l level and Further reveal the role of OMA1/OPA1 Mediate Mitochondrial Fragmentation in Chronic Heart Failure in rat.The EntransterTM-in vivo will be applied to silent the OMA1 and Yme1l and both,to observe the effect in Mitochondrial morphology and cardiac metabolism and cardiac function for the investigation of effective target for CHF.