title: [Role of endogenous and exogenous hydrogen sulfide in acute lung injury induced by LPS in rats].
abstract: OBJECTIVE
  To explore the role of endogenous and exogenous hydrogen sulfide (H2S) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and the underlying mechanisms.
  
  
  METHODS
  120 Sprague-Dawley rats were randomly divided into four groups: control, LPS (instilled intratracheally to induce ALI), NaHS (H2S donor) + LPS, and propargylglycin (PPG) + LPS. Animals were sacrificed at 4 h or 8 h after agent administration. Lung weight/body weight ratio (LW/BW) was measured and calculated. Morphological changes of lung tissues were observed. H2S concentration, NO concentration (NO) and carbon monoxide (CO) level in plasma were tested. Malondialdehyde (MDA) content, CSE activity, inducible nitric oxide synthase (iNOS) activity and hemeoxygenase (HO) activity of the lung were determined. PMN and protein content in BALF were also tested. Immunohistochemisty technique was performed to examine the expression of iNOS and HO-1 protein in lung tissues. The correlation of H2S content with the above indices was analyzed.
  
  
  RESULTS
  Compared with control conditions, severe injuries of lung tissues and a raised LW/BW, MDA content, PMN and protein content in BALF were observed in rats treated with LPS. LPS also lead to a drop in plasma H2S concentration and lung CSE activity. The enzyme activity of iNOS and HO, the protein expression of them and plasma NO, CO level increased after LPS instillation. Administration of NaHS before LPS could attenuated the changes induced by LPS. Pre-administration of PPG exacerbated the injuries induced by LPS, increased PMN and protein content in BALF, the plasma NO level, lung iNOS activity and its protein expression, but there was no prominent variation in CO level, HO activity and HO-1 protein expression compared with those of LPS group. The H2S content was positively correlated with CSE activity, CO content and HO-1activity (r = 0.945-0.987, P < 0.01), and negatively correlated with the other indices (r = -0.994 - -0.943, P < 0.01).
  
  
  CONCLUSIONS
  Downregulation of H2S/CSE was involved in the pathogenesis of acute lung injury induced by LPS. Endogenous and exogenous H2S provided protection against the lung injuries, which might be explained by its anti-oxidative effects, attenuating inflammatory over-reaction in lung induced by PMN,the downregulation NO/iNOS system and the upregulation of CO/HO-1 system.
authors.affiliation: Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050091, China.
authors.forename: Xiao-hong
authors.initials: XH
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.forename: Xin-li
authors.initials: XL
authors.lastname: Huang
authors.forename: Yi-ling
authors.initials: YL
authors.lastname: Ling
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D002248:Carbon Monoxide / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D002248:Carbon Monoxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D006862:Hydrogen Sulfide