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

Abstract

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-1b 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. Hightidal volume ventilation significantly increased the levels of IL-1b, 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.

The Effects of One-lung Ventilation on the Production of Endogenous Melatonin and NLRP3 Inflammasome-Related Inflammatory Cytokines in Patients Undergoing Laparoscopic Esophagectomy: A Prospective Randomized Double-Blind Controlled Study

“…IL-1β and IL-18 were confirmed to be products of NLRP3 inflammasome activation [19]. Furthermore, current studies have demonstrated that NLRP3 inflammasome activation plays a key role in the pathogenesis of VILI in a mouse model [17,18]. Therefore, lung-protective ventilation may inhibit inflammatory responses by inhibiting activation of the NLRP3 inflammasome during OLV.…”

“…Recently, researchers demonstrated that NLRP3 inflammasome activation is important for exacerbating VILI [17,18]. The activation of the NLRP3 inflammasome produces IL-1β and IL-18 [19].…”

The Effects of Protective Ventilation on the Production of Endogenous Melatonin and Prognosis in Patients Undergoing Esophageal Cancer Surgery: A Prospective Randomized Double-Blind Controlled Study

“…Furthermore, current studies have demonstrated that NLRP3 in ammasome activation plays a key role in the pathogenesis of VILI in a mouse model [25,26]. Therefore, lung protective ventilation may inhibit in ammatory responses by inhibiting the activation of the NLRP3 in ammasome.…”

Dexmedetomidine for prevention of postoperative pulmonary complications in patients after oral and maxillofacial surgery with fibular free flap reconstruction:a prospective, double-blind, randomized, placebo-controlled trial

“…This hinders airway which might cause the incident of PPCs as an outcome 24 . Moreover, this type of surgery had long surgical time or mechanical ventilation time (mostly more than 3 hours), which might cause ventilation induced lung injury (VILI) 25 , and had limb ischemia-reperfusion injury due to the use of the tourniquet in the thigh area, which might induce remote lung damage 26 . Except that, after the type of surgery, due to the microvascular reconstruction technique in the neck region, patients are required to stay lying in bed restraining lots of neck movement for at least three days after surgery, which might bring about respiratory muscle complications and mouth ejection and even PPCs 27 .…”