The Preventive And Treatment Effect Of N-acetyl-L-cysteine And Zafirlukast Against Acute Lung Injury

Adult respiratory distress syndrome (ARDS) is a clinical emergency characterized by persistent hypoxima, with a high mobility and mortality. Acute lung injury (ALI) is the fundermental pathological changes of ARDS. The pathogenesis of these two disorders are very inticacy and still unriddled. In clinic, there is no effective treatment methord. Now peaple are aware that these two diseases are kinds of systemic disorders start-uped by many risk-factors involving many cellular factors and inflammatory cells. Inflammatory reaction play the critical role in this process. Leukotrienes and free oxygen radicals play important roles in the inflammatory process and amplify the inflammatory reaction resulting in the lung injury.AIM Zafirlukast is the receptor retardant of leukotrienes and can competively repress the effect of leukotrienes. N-acetylcysteine is a thiol-containing compound that acts as a scavenger of oxygen free radicals and a precursor of glutathione. This experiment is to observe the preventive effect of zafirlukast and treatment eflFect of N-acetylcysteine on ALI.METHODS 32 rabbits were randomly divided into four groups: control group (n=8), LPS group (n=8), LPS+ Zafirlukast group (n=8). LPS+ N-acetylcysteine group (n=8). The LPS group were injected endotoxin( 1ml ?kg"1), control group were injected normal saline (1ml ?kg"1), LPS+ N-acetyl-L-cysteine group were given N-acetyl-L-cysteine (300mg ?kg"1) 2 minutes before being injected endotoxin (1ml ?kg'1) . LPS+ Zafirlukast group were given zafirlukast (20mg ?kg"1) twice before being injected endotoxin (LPS, 1ml "kg"1) half an hour and one hour. Observe the arterial oxygen pressure (PaO2), the pulmonary arterial pressure, count of peripheral-blood leukocytes, NO2" concentration in the BALE, lung index (wet weight /body weight), lung's wet /dry weight ratio (W/D), endothelin-1 in the plasma, count of leukocytes in the lung and had HE staining of the pathological sections.RESULT The pulmonary arterial pressure and NO:" concentration of LPS+NAC group had significant difference with injury group (PO.01). The pulmonary arterial pressure of LPS+ZFL group had significant difference with injury group (PO.01) but NO2" concentration of LPS+ZFL group had no significant difference with injury group (P>0.05). PaOi of both treatment groups significantly improved (P<0.01). Lung index and W/D ratio of both treatment groups were significantly lower than those of the injury group (P<0.01), the count of peripheral-blood leukocytes of both treatment groups was higher than that of injury group (P<0.01). Endothelin-1 in the plasma and count of leukocytes in the lung of both treatment group are lower than those of injury group. HE staining showed that lung injury of both treatment groupsimproved.