Abstract: The aim of this study was to evaluate the protective effect of thalidomide derivative ZSN-12 on acute lung injury induced by oleic acid in mice, and to investigate the possible mechanisms. The results showed that ZSN-12 (200 mg/kg) markedly improved the pathological changes of acute lung injury. The proportion of polymorphonuclear neutrophils (PMN) was reduced by 48% (P<0.01) and the content of nitric oxide (NO) in bronchoalveolar lavage fluid (BALF) was decreased by 33% (P<0.05). ZSN-12 produced significant anti-inflammatory effects in the models of xylene induced ear edema and carrageenan induced paw edema, in which ZSN-12 inhibited ear edema and paw swelling in a dose-dependent manner. The inhibition rates by ZSN-12 dosed at 200, 100, 50 mg/kg were 62%, 43%, and 30% in ear edema, respectively and 60%, 47%, and 33% in paw edema, respectively, at 3 h. Meanwhile, ZSN-12 (10, 5, 1 μmol/L) significantly restrained the ConA-induced T lymphocyte proliferation, with the inhibition rates of 33%, 30% and 22%, respectively (P<0.01). In conclusion, the present study showed that administration of thalidomide derivative ZSN-12 exerted significant protective effect in acute lung injury induced by oleic acid in mice, which may be related to its anti-inflammation effect. ZSN-12 inhibited the effusion of PMN, reduced the release of NO, and suppressed the proliferation of T lymphocyte.

Key words: Thalidomide derivative ZSN-12, Acute lung injury, Anti-inflammation