[The role of hydrogen sulfide in acute lung injury during endotoxic shock and its relationship with nitric oxide and carbon monoxide].
OBJECTIVE
To explore the role of hydrogen sulfide (H2S) in acute lung injury (ALI) during endotoxic shock (ES) and its relationship with nitric oxide (NO) and carbon monoxide (CO).


METHODS
Sixty-four adult male SD rats were randomly divided into 4 equal groups: control group injected with normal saline via the caudal vein, lipopolysaccharide (LPS)-treated group injected with LPS to establish ES model, LPS + NaHS group injected with LPS and sodium hydrosulfide (NaHS, an exogenous H2S donor], and LPS + PPG group injected with LPS and polypropylene glycol (PPG, a H2S synthase inhibitor). The mean artery pressure (MAP) was measured via a polyethylene catheter in the right common carotid artery for 6 h. Then the rats were sacrificed with their lungs taken out to determine the lung water content, lung tissue malonyldialdehyde (MDA), NO, and CO contents, as well as lung tissue cystathionine-gamma-lyase (CSE), myeloperoxidase (MPO), nitric oxide synthase (NOS), and heme oxygenase (HO) activities. The H2S content in blood plasma was detected also. Morphological changes of the lung tissues were observed under light microscope and the index of quantitative assessment (IQA) of lung injury was calculated. Immunohistochemistry and Western blotting were used to detect the lung tissue inducible NOS (iNOS) and HO-1 protein expression.


RESULTS
Compared with the control group, the MAP of the LPS group was significantly lower, the pathological changes in lung tissue was more obvious, and the IQA, lung water content, lung MDA content, lung MPO and CSE activities as well as plasma H2S content were all significantly higher (P < 0.05 or P < 0.01). Compared to the LPS group, the plasma H2S and lung CSE activity of the LPS + NaHS group were higher, the lung injury was more severe, and the MAP was lower. And compared to the LPS group, the MAP of the LPS + PPG group was higher, and the lung injury was milder (both P < 0.05). The eNOS activity in the lung tissue of the LPS group was (5.26 +/- 0.25) Uxmg(-1)xprot(-1), significantly lower than that of the control group [(6.45 +/- 0.42) Uxmg(-1)xprot(-1)]; and the iNOS activity and NO content of the LPS group were (12.6 +/- 0.6) Uxmg(-1)xprot(-1) and (144 +/- 25) micromol/L respectively, both higher than those of the control group [(10.5 +/- 0.7) Uxmg(-1)xprot(-1) and (68 +/- 5) micromol/L respectively] (P < 0.05 or P < 0.01). Compared with the LPS group, the lung tissue eNOS activity of the LPS + PPG group was significantly higher, and the iNOS activity [(10.2 +/- 0.4) Uxmg(-1)xprot(-1)], iNOS protein expression, and NO content [(74 +/- 5) micromol/L]were all significantly lower (P < 0.05 or P < 0.01). Compared with the LPS group, the lung tissue eNOS activity of the LPS + NaHS group [(4.81 +/- 0.23) Uxmg(-1)xprot(-1)] was significantly lower, and the iNOS activity [(14.6 +/- 0.4) Uxmg(-1)xprot(-1)], iNOS protein expression, and NO content [(217 +/- 18) micromol/L] were significantly higher (P < 0.05 or P < 0.01). The lung tissue HO activity [(173 +/- 31) pkat/g], HO protein expression, and CO content [(3.63 +/- 0.24)%] of the LPS group were all significantly higher than those of the control group [(125 +/- 22) pkat/g, (2.48 +/- 0.33)%, both P < 0.05], and the LPS + PPG group [(88 +/- 17) pkat/g, (2.98 +/- 0.23)%, both P < 0.05]. Compared to the LPS group, the lung tissue HO activity [(263 +/- 37) pkat/g], HO protein expression, and CO content [(4.35 +/- 0.32)%] of the LPS + NaHS group were all significantly higher (all P < 0.05).


CONCLUSIONS
The increase of H(2)S generation participates in the lung tissue injury during ES and this event is related to eNOS activity decrease, iNOS activity increase that causes the production of large amount of NO. H2S up-regulates the HO-1/CO system in the lung tissues during ES, which may be the endogenous compensatory response against the injury.
Huang
Xin-li
XL
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.
Zhou
Xiao-hong
XH
Wei
Peng
P
Xian
Xiao-hui
XH
Ling
Yi-ling
YL
D055371:Acute Lung Injury / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002248:Carbon Monoxide / Q000097:blood / Q000378:metabolism*; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000097:blood / Q000378:metabolism*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D013440:Sulfides / Q000008:administration & dosage / Q000494:pharmacology
D008070:Lipopolysaccharides; D013440:Sulfides; D009569:Nitric Oxide; D008315:Malondialdehyde; D002248:Carbon Monoxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide