细胞焦亡在硫化氢抗心力衰竭中的作用机制研究

In recent years, the role of pyroptosis in the process of heart failure by everyone's attention. Pyroptosis is a recently defined form of programmed cell death that occurs with the release of numerous proinflammatory factors, leading to and exacerbating the inflammation of the tissue. At the same time, inflammatory response and oxidative stress play a crucial role in the development of heart failure, and they interact with each other to promote the occurrence and development of heart failure. Therefore, inflammatory response and oxidative stress may be important strategies for the treatment of heart failure . Hydrogen sulfide (H2S), a gas signaling molecule, is produced by cystathionine-γ-lyase (CSE) in the cardiovascular system and plays an important role by inhibiting inflammatory reactions and oxidative stress during heart failure. However, its mechanism of pyroptosis is unclear. This project intends to clarify the pyroptosis inhibitory effect and mechanism of the active gas H2S / CSE signaling system, and through NLRP3 inhibition and mechanism, anti-heart failure mechanism. The study of H2S / CSE mechanism of anti-heart failure will start from the pathway of pyroptosis, with mitochondrial function, energy metabolism and apoptosis as the starting point, and finally determine the target.

近年来，细胞焦亡在心衰进程中的作用受到大家关注。细胞焦亡是最近定义的一种程序性细胞死亡形式，其发生伴随着大量促炎性因子的释放，进而导致和加重组织炎症反应。同时，炎症反应和氧化应激在心力衰竭发展过程中发挥至关重要作用，同时二者又相互作用促进心力衰竭的发生和发展，因此，炎症反应和氧化应激可能成为治疗心力衰竭的重要策略。气体信号分子硫化氢（H2S）在心血管系统中由胱硫醚-γ-裂解酶（CSE）产生并通过抑制心力衰竭过程中的炎症反应、氧化应激作用等发挥重要作用。但其对细胞焦亡其机制还不清楚；本项目拟阐明活性气体H2S/CSE信号系统的细胞焦亡抑制作用及机制、通过NLRP3抑制作用及机制、抗心力衰竭机制。H2S/CSE抗心力衰竭机制的研究将从细胞焦亡途径入手，以线粒体功能、能量代谢和细胞凋亡作用为切入点，最终确定作用靶点。

近年来，细胞焦亡在心衰进程中的作用受到大家关注。细胞焦亡是最近定义的一种程 序性细胞死亡形式，其发生伴随着大量促炎性因子的释放，进而导致和加重组织炎症反应 。同时，炎症反应和氧化应激在心力衰竭发展过程中发挥至关重要作用，同时二者又相互 作用促进心力衰竭的发生和发展，因此，炎症反应和氧化应激可能成为治疗心力衰竭的重 要策略。气体信号分子硫化氢（H2S）在心血管系统中由胱硫醚-γ-裂解酶（CSE）产生并 通过抑制心力衰竭过程中的炎症反应、氧化应激作用等发挥重要作用。本项目从细胞和动物模型阐明活性气体H2S/CSE信号系统的细胞焦亡抑制作用及机制、通 过NLRP3抑制作用及机制、抗心力衰竭机制。H2S/CSE抗心力衰竭机制的研究将从细胞焦亡 途径入手，以线粒体功能、能量代谢和细胞凋亡作用为切入点，最终确定作用靶点。