Dexmedetomidine protects against lung injury induced by limb ischemia‐reperfusion via the TLR4/MyD88/NF‐κB pathway

Abstract

Dexmedetomidine (DEX) can protect the lung from ischemia-reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. The aims of this study were to determine whether DEX attenuates lung injury following lower extremity I/R and to investigate the related toll-like receptor 4 (TLR4) signaling pathway. Twenty-eight SD rats were divided into four groups (n = 7): Sham, I/R, I/R + DEX (25 μg/kg prior to ischemia), and I/R + DEX + Atip (250 μg/kg atipamezole before DEX treatment). Lower extremity I/R was induced by left femoral artery clamping for 3 hours and followed by 2 hours reperfusion. Quantitative alveolar damage and the wet/dry (W/D) ratio were calculated. Interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)α in the bronchoalveolar lavage fluid (BALF) and serum and myeloperoxidase (MPO) in the lung were measured. The TLR4 and MyD88 mRNA expression levels were measured by RT-PCR, nuclear factor (NF)-κB, and phosphorylated NF-κB by western blot, respectively. Quantitative alveolar damage, W/D ratio, MPO, BALF and serum IL-1, IL-6, and TNF-α, and TLR4, MyD88, NF-κB, and p-NF-κB expression significantly increased in the I/R group relative to the Sham group. DEX preconditioning significantly reduced lung edema, and histological injury relative to the I/R group. Serum and BALF IL-1, IL-6, and TNF-α levels, MPO activity and TLR4, MyD88, NF-κB, and p-NF-κB expression were also significantly reduced in the I/R + DEX group compared with the I/R group. Atipamezole partially reversed all the aforementioned effects. DEX preconditioning protects the lungs against lower extremity I/R injury via α2-adrenoceptor-dependent and α2-adrenoceptor-independent mechanisms. It also suppresses the TLR4 pathway and reduces inflammation. K E Y W O R D S acute lung injury, dexmedetomidine, limb ischemia/reperfusion injury, toll-like receptor 4

Protective Effects of Ischemic Postconditioning on Livers in Rats with Limb Ischemia-Reperfusion via Glycogen Synthase Kinase 3 beta (GSK-3β)/Fyn/Nuclear Receptor-Erythroid-2-Related Factor (Nrf2) Pathway

“…SOD is an important antioxidant enzyme in vivo and can scavenge superoxide anion free radicals and prevent cell damage caused by membrane lipid peroxidation. MPO is a marker enzyme of PMN, and its activity can reflect the degree of PMN infiltration and the release of inflammatory mediators in liver tissue [ 32 , 33 ]. MDA is a product of lipid peroxidation and an index used to measure the degree of tissue peroxidation damage.…”

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 .…”

Pretreatment with dexmedetomidine alleviates lung injury in a rat model of intestinal ischemia reperfusion

“…experiment 1 was designed to test the effects of deX (Jiangsu Hengrui Medicine co., ltd., Jiangsu, china) pretreatment on pathological damage to the lung during iir and to select the optimal drug dose. at present, the majority of researchers have selected 25-50 µg/kg deX (injected intraperitoneally) in order to study its protection against ischemia reperfusion injury (18)(19)(20). intravenous injection of deX always requires small doses ranging from 1 to 10 µg/kg (21,22).…”