ABSTRACT
Objective To observe the effect of apigenin on acute lung injury (ALI) induced by lipopolysaccharide(LPS)in mice,and to discuss its possible mechanism. Methods Forty healthy male Kunming mice were randomly divided using random number table into control group,model group and low,medium,high dose groups of apigenin intervention,and each group consisted of 8 mice. The model of ALI was reproduced by intraperitoneal injection of 5 mg/kg LPS. Mice of the low,medium and high-dose intervention groups were given intraperitoneal injection of apigenin 10,25,50 mg/kg,respectively,1 hour before LPS modeling. Pathological changes in right upper lobe of lung tissue were examined after hematoxylin and eosin(HE)staining and pathology score was observed at 6 hours after modeling. Right inferior lung was weighed to measured wet/dry ratio(W/D). Intercellular adhesion molecule-1(ICAM-1)and tumor necrosis factor-α(TNF-α)in serum and bronchoalveolar lavage fluid (BALF)were determined by enzyme linked immunosorbent assay(ELISA). The mRNA expressions of p38 mitogen-activated protein kinase(p38MAPK),ICAM-1,and TNF-α were determined by reverse transcription-polymerase chain reaction(RT-PCR). Results Compared with control group,lung W/D ratio in model group was significantly increased(17.79±2.89 vs. 5.56±0.37,P<0.05),and the pathology score was significantly elevated(10.32±0.23 vs. 1.87±0.54,P<0.05),ICAM-1 and TNF-α contents,in serum and BALF were increased〔ICAM-1(ng/L) in serum:21.4±2.7 vs. 14.3±3.5,TNF-α(ng/L)in serum:254.8±10.6 vs. 142.3±13.7;ICAM-1(ng/L)in BALF:20.3±2.4 vs. 11.5±3.2,TNF-α(ng/L)in BALF:230.3±5.8 vs. 110.5±11.2,all P<0.05〕,and the mRNA expressions of p38MAPK,ICAM-1 and TNF-α were also increased significantly(the mRNA expression of p38MAPK,ICAM-1 and TNF-αwere 4.42±0.37,4.89±0.27,3.28±0.13,respectively,all P<0.05). Different doses of apigenin could obviously alleviate the damaging effect to the lung,and the most obvious effect was seen in the medium dose group,in which lung W/D ratio was 13.28±1.21,ICAM-1 in serum was(18.5±4.3)ng/L,TNF-αin serum was(169.4±20.8)ng/L,ICAM-1 in BALF was(17.8±3.5)ng/L,TNF-αin BALF was(150.4±7.1)ng/L, the mRNA expression of p38MAPK,ICAM-1 and TNF-αin lung tissue was 2.99±0.28,3.97±0.17,2.87±0.27, respectively. Statistically significant difference was found when they were compared with that of model group(P<0.05 or P<0.01). Conclusion Different doses of apigenin have some antagonistic effect against LPS in producing ALI in mice,the best improvement effect was seen in the medium dose group,and the protective effect may be related to inhibition of p38MAPK signaling pathway activity and reduction of pro-inflammatory factors such as TNF-αand ICAM-1 expression.