Effects And Mechanism Of L-arginine On Acute Lung Injury Induced By LPS

Objective :To observe the changes of ET-1 and NO in endothelial system and the cytokines in the model of acute lung injury induced by lipopolysaccharide,and to investigate the mechanisms of L-Arginine protects against acute lung injury induced by LPS.Methods:45 adult male Wistar rats were randomly divided into three groups as follows:NS group, LPS group and L-Arg group. L-Arginine was intraperitoneally injected before LPS infused to made the ALI model. Five rats in each group were killed at 2h?6h and 24 h, meanwhile the Pa O2?W/D and protein concentration in BALF were determined at different point of time;serum were collected to determine TNF-? ?IL-6?IL-10 by enzyme-linked immunosorbent assay(ELISA). Real time PCR and immunocytochemistry(IHC) were used to detect the m RNA and protein expression of i NOS and ET-1. The concentration of NO was determined by nitrate reductase method.The pathology changes of lung tissue were observed under light microscope.Results:(1)Rats in the LPS group had sustained hypoxemia, with Pa O2 decreasing as time passed. There was a significant increase in W/D, in protein concentration of BALF(P<0.05). Under light microscope, interstitial tissue of the lung showed exudation, edema,a great quantity of inflammatory cells accumulation and pulmonary alveolis were damaged in the LPS group. Those items in the L-Arg group had a significant improvement than those in LPS group(P<0. 05).(2)The secretion of TNF-?,IL-6,IL-10 and NO increased more remarkably in the blood serum of LPS group than those of NS group, meanwhile in L-Arg group those items were significantly decreased except the increase of NO(P<0.05);(3)Pulmonary expression of m RNA and protein of ET-1 and i NOS increased gradually and reached the high point at 24 h in LPS group after modeling. With the aggravation of pulmonary injury, ET-1 was positively expressed in vascular endothelial cells, Airway epithelial cells, macrophages and polymorphonuclear neutrophil, etc.; Meanwhile i NOS was positively expressed in the samilar area of lung. Compared with LPS group, the m RNA and protein expression of ET-1 and i NOS were significantly decreased in L-Arg group at the same time after modeling(P<0.05).Conclusion:Pretreatment of L- Arginine could alleviate acute lung injury induced by LPS. The protection mechanism maybe to down-regulate ET-1and up-regulate NO, to improve pulmonary circulation, and to inhibit excessive inflammatory reaction, etc.