[Effect of L-Arg on inflammatory reaction and nuclear factor-kappa B signal pathway in the acute lung injury in rats induced by lipopolysaccaride].
OBJECTIVE
To investigate the effects and the mechanisms of L-Arginine (L-Arg), the critical substrate for nitric oxide (NO) production, on pulmonary inflammatory cytokine expression and Nuclear Factor-kappa B signal pathway in a model of lipopolysaccharide (LPS) induced acute lung injury (ALI).


METHODS
Model of ALI was induced by injection (iv) with LPS 5 mg/kg in male SD rats. L-Arg (500 mg/kg ip) was administrated at 3 h or 6 h after LPS injection respectively for 3 h, and the rats were killed at 6 h or 9 h after saline (control) or LPS injection. The expression and the translocation of NF-kappa B P65 in lung tissue were detected with immunohistochemisty (IHC). The gene expression of intercellular adhesion molecule-1 (ICAM-1) was examined by RT-PCR. The concentrations of TNF-alpha and IL-6 in lung tissue were respectively evaluated by radioimmunoassay. The pathological changes of lung tissue were observed by light microscope.


RESULTS
Compared with LPS group, treatment with L-Arg at 3 h after LPS significantly decreased the expression of NF-kappa B protein. The concentrations of TNF-alpha and IL-6 in lung tissue were significantly decreased and the lung damage was inproved respectively compared with that of the LPS (3 h + 3 h) group. The lung damage was alleviated in L-Arg (3 h + 3 h) group.


CONCLUSIONS
Relatively early administration of L-Arg might protect lung from LPS-induced injury by inhibiting NF-kappa B activation and subsequently inhibiting the NF-kappa B-mediated release of inflammatory factors.
Li
Li-ping
LP
Insitute of Materia Medica, Hebei Academy of Medical Sciences, Shijiazhuang 050021, China.
Zhang
Jian-xin
JX
Li
Lan-fang
LF
D055371:Acute Lung Injury / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D000818:Animals; D001120:Arginine / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000503:physiopathology*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D001120:Arginine