Oxidative stress is implicated in the pathogenesis of influenza virus infection. Increasing evidences show that transient receptor potential melastatin 2 (TRPM2), a Ca²⁺-permeable non-selective cation channel, plays an important role in the pathomechanism of reactive oxygen species (ROS)-coupled diseases. The present study investigated the role of TRPM2 in pulmonary microvascular endothelial cells (PMVECs) during H9N2 influenza virus infection. We knocked down TRPM2 in PMVECs using TRPM2 shRNA lentiviral particles. Subsequently, we utilized enzyme-linked immunosorbent assay and flow cytometry to compare ROS levels, DNA damage, mitochondrial integrity, apoptosis, and inflammatory factors between control and TRPM2-knockdown PMVECs following H9N2 influenza virus infection. Inhibition of TRPM2 channels reduced H9N2 virus-induced intracellular ROS production, decreased DNA damage, and inhibited H9N2-induced cellular apoptosis. This study shows that the inhibition of TRPM2 channels may protect PMVECs from the damage caused by H9N2 virus infection. Our results highlight the importance of TRPM2 in modulating ROS production, apoptosis, mitochondrial dysfunction, cytokine expression, and DNA damage in H9N2 virus-infected PMVECs, and suggest that TRPM2 may be a potential antiviral target.

氧化应激与流感病毒感染的发病机理有关。越来越多的证据表明，瞬态受体电位褪黑素2（TRPM2），一种Ca ²⁺可渗透的非选择性阳离子通道，在活性氧（ROS）耦合疾病的发病机理中起重要作用。本研究调查了TRPM2在H9N2流感病毒感染过程中在肺微血管内皮细胞（PMVEC）中的作用。我们使用TRPM2 shRNA慢病毒颗粒敲除了PMVEC中的TRPM2。随后，我们利用酶联免疫吸附测定和流式细胞术比较了H9N2流感病毒感染后对照和TRPM2敲除PMVEC之间的ROS水平，DNA损伤，线粒体完整性，细胞凋亡和炎症因子。抑制TRPM2通道减少了H9N2病毒诱导的细胞内ROS的产生，减少了DNA损伤，并抑制了H9N2诱导的细胞凋亡。这项研究表明，TRPM2通道的抑制作用可以保护PMVEC免受H9N2病毒感染引起的损害。我们的结果强调了TRPM2在调节H9N2病毒感染的PMVEC中的ROS产生，凋亡，线粒体功能障碍，细胞因子表达和DNA损伤中的重要性，并暗示TRPM2可能是潜在的抗病毒靶标。