从线粒体动力学探讨益气温阳中药提高心力衰竭运动耐量的机制研究

The main purpose of traditional Chinese medicine to improve heart failure is to improve the patient's exercise tolerance. Exercise tolerance is closely related to mitochondria. Combined with the results of pre-research hypotheses: "Yiqi Wenyang traditional Chinese medicine can improve the patient's myocardial cell mitochondrial structure and function, optimize myocardial energy metabolism, improve heart failure in patients with exercise tolerance.The main target is from the structural and functional aspects of mitochondrial metabolism" The On the hypothesis, the mitochondrial damage and repair mechanism, starting with mitochondrial structural changes and functional changes as the starting point, through structural monitoring of ultrastructural, membrane potential, mitochondrial permeability transition pore opening, and respiratory function, oxygen consumption And the effect of mitochondrial function on mitochondrial function and mitochondrial function were investigated by laser confocal microscopy, RT-PCR, Westen-blot and Elisa. Repair mechanism to mitochondrial dynamics as the main means of technology, through the fusion and split the way to repair the damage, proof of Qi and Yang Chinese medicine to promote the repair of the target. The mechanism of mitochondria in Chinese herbal medicine was also revealed, which provided a new idea for revealing the mechanism of traditional Chinese medicine against heart failure.

中药改善心力衰竭的主要目的是提高患者的运动耐量。运动耐量与线粒体密切相关。结合前期研究结果提出假说：“益气温阳中药能够通过改善患者心肌细胞线粒体结构和功能，优化心肌能量代谢，提高心衰患者运动耐量。主要作用靶点在于从结构和功能两方面调节线粒体代谢”。围绕假说，课题从线粒体损伤和修复机制入手，以线粒体结构改变和功能变化为切入点，通过超微结构、膜电位、线粒体通透性转换孔开放程度的结构性检测，以及呼吸功能、耗氧率、钙瞬变调节的功能检测，利用激光共聚焦显微镜、RT-PCR、Westen-blot、Elisa等技术手段，探索益气温阳中药改变线粒体结构、提高线粒体功能的作用靶点。修复机制研究以线粒体动力学为主要技术手段，通过融合与分裂途径修复损伤，证明益气温阳中药促进修复的靶点。全面揭示了益气温阳中药对线粒体的作用机制，为揭示中药抗心力衰竭的机制提供新思路。

运动耐量与线粒体密切相关，课题从线粒体损伤和修复机制入手，通过超微结构、膜电位、线粒体通透性转换孔开放程度的结构性检测，以及呼吸功能、耗氧率、钙调节的功能检测，利用激光共聚焦显微镜、RT-PCR、Westen-blot、Elisa等技术手段，探索益气温阳中药改变线粒体结构、提高线粒体功能的作用靶点。实验研究发现：益气温阳中药可显著降低心衰大鼠血清BNP水平，提升左室射血分数；改变应激状态下心肌细胞的超微结构，维持线粒体结构的稳定；升高心衰大鼠的心肌细胞线粒体膜电位；改善心衰大鼠心肌线粒体膜通道通透性；改善线粒体复合物的呼吸功能，提高心肌内源性抗氧化酶的活性，间接抑制ROS的产生和氧化/抗氧化系统的失衡；有效提高CHF小鼠心肌组织中ATP1a1的表达，增强Na+-K+ ATPase的活性和产生，提高ATP的含量，改善心脏的能量代谢及心肌细胞中K+浓度失衡状态；抑制衰竭心肌细胞NCX1表达、提高SERCA2表达；激活Nrf2/HO-1通路以及调节线粒体融合、分裂的平衡，抑制心肌细胞凋亡，保护受损心肌细胞。此外，益气温阳中药显示可通过降低NLRP3炎症小体介导的焦亡相关蛋白及IL-18、IL-1β炎症因子的表达有效抑制慢性心衰。通过以上研究，全面揭示了益气温阳中药对线粒体的作用机制，证明益气温阳中药促进线粒体修复的靶点，从线粒体动力学和细胞焦亡两个途径为中药抗心力衰竭的机制提供了新思路。