title: H₂S protecting against lung injury following limb ischemia-reperfusion by alleviating inflammation and water transport abnormality in rats.
abstract: OBJECTIVE
  To investigate the effect of H₂S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism.
  
  
  METHODS
  Wistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide (NaHS) group and IR+ DL-propargylglycine (PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NaHS (0.78 mg/kg) as exogenous H₂S donor and PPG (60 mg/kg) which can suppress endogenous H₂S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 (AQP₁), aquaporin-5 (AQP₅) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 (TLR₄), myeloid differentiation primary-response gene 88 (MyD88) and p-NF-κB as indexes of inflammation.
  
  
  RESULTS
  LIR induced lung injury was accompanied with upregulation of TLR₄-Myd88-NF-κB pathway and downregulation of AQP1/AQP₅. NaHS pre-treatment reduced lung injury with increasing AQP₁/AQP₅ expression and inhibition of TLR₄-Myd88-NF-κB pathway, but PPG adjusted AQP₁/AQP₅ and TLR4 pathway to the opposite side and exacerbated lung injury.
  
  
  CONCLUSIONS
  Endogenous H₂S, TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ were involved in LIR induced lung injury. Increased H₂S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ expression to reduce inflammatory reaction and lessen pulmonary edema.
authors: Department of Comprehensive Surgery in South Building, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Medical School, Beijing 100853, China.
authors: Qi Ying Chun
authors: QY
authors: Qi
authors: Department of Comprehensive Surgery in South Building, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Medical School, Beijing 100853, China.
authors: Wen
authors: W
authors: Chen
authors: Department of Comprehensive Surgery in South Building, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Medical School, Beijing 100853, China.
authors: Xiao Ling
authors: XL
authors: Li
authors: Department of Comprehensive Surgery in South Building, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Medical School, Beijing 100853, China.
authors: Yu Wei
authors: YW
authors: Wang
authors: Department of Comprehensive Surgery in South Building, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Medical School, Beijing 100853, China.
authors: Xiao Hua
authors: XH
authors: Xie
mesh_terms: D055371:Acute Lung Injury / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D020346:Aquaporins / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000209:etiology / Q000473:pathology; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000517:prevention & control; D008168:Lung / Q000473:pathology; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014867:Water / Q000378:metabolism
chemical_list: D020346:Aquaporins; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014867:Water; D006862:Hydrogen Sulfide
keywords: Aquaporin-1; Aquaporin-5; Hydrogen sulfide; Limb Ischemia-reperfusion; Nuclear Factor-κB; Toll-like receptors