OBJECTIVETo 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).

METHODSModel 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.

RESULTSCompared 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.

CONCLUSIONRelatively 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.