Open AccessDexmedetomidine protects against lung injury induced by limb ischemia‐reperfusion via the TLR4/MyD88/NF‐κB pathway
Author(s) -
Xue BinBin,
Chen BaiHui,
Tang YaNing,
Weng ChengWei,
Lin LiNa
Publication year - 2019
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1002/kjm2.12115
Subject(s) - medicine , tlr4 , bronchoalveolar lavage , myeloperoxidase , reperfusion injury , lung , tumor necrosis factor alpha , ischemia , dexmedetomidine , western blot , anesthesia , pharmacology , endocrinology , receptor , inflammation , biology , biochemistry , sedation , gene
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.