Oxidative stress promotes ventilator-induced lung injury through activating NLRP3 inflammasome and TRPM2 channel.

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 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 duanyu1670 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.

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