TRPM2在H9N2猪流感病毒感染致小鼠肺微血管内皮细胞损伤的作用机制

It has a very important effect of oxidative stress on acute lung injury induced by influenza virus infection. Therefore, the research on intervening oxidative stress aiming to alleviate the lung injury caused by influenza virus infection has become a topic of investigation in this field. This project is mainly to investigate the effect of transient receptor potential M2 (TRPM2), a multifunctional ion channel for oxidative stress sensing, on mice pulmonary microvascular endothelial cells (PMVEC) damage induced by H9N2 subtype swine influenza virus (H9N2-SIV). Firstly, the experiment system of TRPM2-siRNA PMVEC and TRPM2 knockout (TRPM2-/-) mice was built, and then investigated the relationship between TRPM2 ion channel mediated Ca2+ influx,apoptosis and PMVEC disruption following oxidative stress induced by H9N2-SIV in the above experiment system. Secondly, the TRPM2 antagonist was used to intervene the PMVEC damage in the acute lung induced by H9N2-SIV. Not only did this research reveal the effect of TRPM2 ion channels on the PMVEC disruption following oxidative induced by H9N2-SIV, but also lay a foundation of drug target for intervention and treatment of acute lung injury induced by influenza virus. In addition, it will further understand pathological biology about animal influenza, offer a new idea on the research in this field, and enrich the theory of cellular signal transduction.

氧化应激在流感病毒致肺损伤中起着重要作用，通过干预其诱导的肺损伤已成为研究的热点之一。本项目主要研究氧化应激敏感性离子通道-瞬时受体电位M2（TRPM2)在H9N2亚型猪流感病毒（H9N2-SIV)致小鼠肺微血管内皮细胞（PMVEC)损伤中的作用机制。首先，构建TRPM2-siRNA小鼠PMVEC和TRPM2基因敲除小鼠试验系统，以此探讨TRPM2离子通道介导Ca2+内流、细胞凋亡与H9N2-SIV致PMVEC损伤的关系；其次，在上述试验系统内研究TRPM2拮抗剂对H9N2-SIV感染致小鼠急性肺损伤中PMVEC损伤的影响。本研究不仅初步揭示TRPM2离子通道在H9N2-SIV诱导小鼠PMVEC损伤中的作用，为筛选药物干预/治疗流感病毒诱导肺损伤的靶点奠定基础，而且可以进一步加深对动物流感病理生物学的认识，为该领域的研究提供一种新的思路，对充实细胞转导理论也具有普遍的科学意义。

氧化应激在流感病毒致肺损伤中起着重要作用，通过干预其诱导的肺损伤已成为研究的热点之一。本项目主要研究氧化应激敏感性离子通道-瞬时受体电位M2（TRPM2)在H9N2亚型猪流感病毒（H9N2-SIV)致小鼠肺微血管内皮细胞（PMVEC)损伤中的作用机制。首先，构建TRPM2-siRNA小鼠PMVEC和TRPM2基因敲除小鼠试验系统，以此探讨TRPM2离子通道介导Ca2+内流、细胞凋亡与H9N2-SIV致PMVEC损伤的关系；其次，在上述试验系统内研究TRPM2拮抗剂对H9N2-SIV感染致小鼠急性肺损伤中PMVEC损伤的影响。本研究不仅初步揭示TRPM2离子通道在H9N2-SIV诱导小鼠PMVEC损伤中的作用，为筛选药物干预/治疗流感病毒诱导肺损伤的靶点奠定基础，而且可以进一步加深对动物流感病理生物学的认识，为该领域的研究提供一种新的思路，对充实细胞转导理论也具有普遍的科学意义。