[The mechanisms of carbon monoxide inhalation on the apoptosis of pulmonary cells in rats with acute lung injury induced by lipopolysaccharide].
OBJECTIVE
To investigate the effects of carbon monoxide (CO) inhalation on the apoptosis of pulmonary cells in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS) and to investigate its mechanisms.


METHODS
Eighteen male SD rats were randomly divided into three groups. The ALI group received LPS 5 mg/kg intravenously, while the control group received normal saline, and the CO inhalation group received an inhalation of 2.5 x 10(-4) CO (V/V) after ALI induced by LPS 5 mg/kg. The animals were sacrificed by exsanguinations and lung tissue was harvested at 3 h of observation for determination of the heme oxygenase-1 (HO-1) mRNA with semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), the level of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 with enzyme-linked immunosorbent assay (ELISA) and the maleic dialdehyde (MDA) concentration, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity with chemical methods. The extent of cell apoptosis was observed by using the flow cytometric method.


RESULTS
The change of the levels of HO-1 mRNA, TNF-alpha, IL-6, IL-10, MDA, MPO, SOD and apoptotic cells of the ALI group was significant as compared with the control group [1.002 +/- 0.004, (0.47 +/- 0.06) pg/mg prot, (0.49 +/- 0.12) pg/mg prot, (0.42 +/- 0.08) pg/mg prot, (0.79 +/- 0.14) nmol/mg prot, (6.0 +/- 1.0) U/mg prot, (74 +/- 7) U/mg prot, (0.12 +/- 0.03)%, P < 0.05 or < 0.01], and lung injury was severe. The levels of TNF-alpha, IL-6, MDA, MPO, and apoptotic cells of the CO inhalation group [(0.91 +/- 0.25) pg/mg prot, (0.64 +/- 0.05) pg/mg prot, (1.02 +/- 0.23) nmol/mg prot, (7.2 +/- 1.6) U/mg prot, (1.60 +/- 0.34)%] were decreased, while HO-1, IL-10 and SOD expression [5.433 +/- 0.921, (0.26 +/- 0.07) pg/mg prot, (60 +/- 10) U/mg prot] were increased compared with the ALI group [(1.48 +/- 0.23) pg/mg prot, (1.16 +/- 0.26) pg/mg prot, (1.27 +/- 0.33) nmol/mg prot, (8.2 +/- 1.5) U/mg prot, (3.18 +/- 0.51)%, 3.081 +/- 0.823, (0.15 +/- 0.03) pg/mg prot, (51 +/- 7) U/mg prot, P < 0.05 or < 0.01], and lung injury was attenuated.


CONCLUSIONS
CO inhalation protects lung from injury by regulating oxidative/anti-oxidative and inflammatory/anti-inflammatory disorders, inhibiting excessive cell apoptosis and up-regulating HO-1 expression, which may play an important role in the pathogenesis of LPS-induced ALI.
Liu
Shao-hua
SH
Intensive Care Unit, the First Affiliated Hospital of Nanjing Medicial University, Nanjing 210029, China.
Ma
Ke
K
Xu
Bing
B
Xu
Xin-rong
XR
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002248:Carbon Monoxide / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D008070:Lipopolysaccharides; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1