a Department of Anesthesiology, Qilu Hospital of Shandong University , Jinan , Shandong , China.
b Department of Anesthesiology, Zibo Center Hospital of Shandong , Zibo , Shandong , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3448-3455. doi: 10.1080/21691401.2019.1652631.
Ventilator has been widely used for life support, but ventilator-induced lung injury (VILI) is still a major problem. Oxidative stress has been considered as a key contributor for VILI, but the specific mechanism remains unclear. The expression of NLRP3 inflammasome in cells and inflammatory factors in the supernatant were measured. Mitochondrial ROS and TRPM2 channel currents were investigated using flow cytometry and Patch-clamp technique, respectively. TRPM2 and NLRP3 mice were used for animal experiments. Lung tissues were stained by HE and the wet-dry ratio, bronchoalveolar lavage fluid (BALF) protein, MPO (marrow peroxidase), NLRP3 inflammasome were also investigated. Knockdown of NLRP3 or Caspase-1 or treatments with SS-31 or YVAD inhibited the expression of the NLRP3 inflammasome, and reduced IL-1β and IL-18 levels in cell supernatant. These treatments suppressed the production of ROS and lowered the TRPM2 channel currents, but Rotenone exerted an opposite effect. High-tidal volume ventilation significantly increased the levels of IL-1β, IL-18, NLRP3 inflammasome, wet-dry ratio of lung, MPO and BALF protein. However, these parameters were down-regulated in TRPM2 and NLRP3 mice. These parameters were suppressed in TRPM2 and NLRP3 mice indicate that oxidative stress might promote VILI through activating NLRP3 inflammasome and TRPM2 channel.
呼吸机被广泛应用于生命支持，但呼吸机相关性肺损伤（VILI）仍然是一个主要问题。氧化应激被认为是 VILI 的一个关键因素，但具体机制仍不清楚。测量细胞中 NLRP3 炎性小体的表达和上清液中炎症因子的水平。使用流式细胞术和膜片钳技术分别研究线粒体 ROS 和 TRPM2 通道电流。使用 NLRP3 和 TRPM2 敲除小鼠进行动物实验。对肺组织进行 HE 染色，并检测湿干比、支气管肺泡灌洗液（BALF）蛋白、髓过氧化物酶（MPO）、NLRP3 炎性小体。NLRP3 或 Caspase-1 的敲低或 SS-31 或 YVAD 的处理抑制了 NLRP3 炎性小体的表达，并降低了细胞上清液中 IL-1β 和 IL-18 的水平。这些处理抑制了 ROS 的产生并降低了 TRPM2 通道电流，但鱼藤酮则产生相反的效果。大潮气量通气显著增加了 IL-1β、IL-18、NLRP3 炎性小体、肺湿干比、MPO 和 BALF 蛋白的水平。然而，这些参数在 TRPM2 和 NLRP3 敲除小鼠中均下调。这些参数在 TRPM2 和 NLRP3 敲除小鼠中受到抑制表明，氧化应激可能通过激活 NLRP3 炎性小体和 TRPM2 通道来促进 VILI。
