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.%目的：观察芹菜素对脂多糖（LPS）诱导小鼠急性肺损伤（ALI）的影响，探讨其可能的作用机制。方法将40只健康雄性昆明小鼠按随机数字表法分为对照组、模型组及芹菜素低、中、高剂量组，每组8只。采用腹腔注射LPS 5 mg/kg制备ALI模型；芹菜素低、中、高剂量组分别于制模前1 h腹腔注射芹菜素10、25、50 mg/kg进行干预。制模后6 h进行指标检测，取右肺上叶行苏木素-伊红（HE）染色观察肺组织病理改变并对其进行病理评分，取右肺下叶称重测湿/干质量（W/D）比值，酶联免疫吸附试验（ELISA）检测血清及支气管肺泡灌洗液（BALF）中细胞间黏附分子-1（ICAM-1）和肿瘤坏死因子-α（TNF-α）的含量，逆转录-聚合酶链反应（RT-PCR）检测p38丝裂素活化蛋白激酶（p38MAPK）、ICAM-1和TNF-α的mRNA表达。结果与对照组比较，模型组肺W/D比值增高（17.79±2.89比5.56±0.37，P＜0.05），肺组织病理评分增加（分：10.32±0.23比1.87±0.54，P＜0.05），血清及BALF中ICAM-1、TNF-α含量升高〔血清中ICAM-1（ng/L）：21.4±2.7比14.3±3.5，TNF-α（ng/L）：254.8±10.6比142.3±13.7；BALF 中 ICAM-1（ng/L）：20.3±2.4比11.5±3.2，TNF-α（ng/L）：230.3±5.8比110.5±11.2，均 P＜0.05〕，且 p38MAPK、ICAM-1和 TNF-α的mRNA表达亦明显升高（以对照组为1，p38MAPK、ICAM-1、TNF-α的相对表达量分别为4.42±0.37、4.89±0.27、3.28±0.13，均P＜0.05）；不同剂量芹菜素可减轻上述损伤效应，以中剂量组改善最为明显，肺W/D比值为13.28±1.21，血清中ICAM-1为（18.5±4.3）ng/L，TNF-α为（169.4±20.8）ng/L，BALF中ICAM-1为（17.8±3.5）ng/L，TNF-α为（150.4±7.1）ng/L，肺组织p38MAPK、ICAM-1、TNF-α的mRNA表达分别为2.99±0.28、3.97±0.17、2.87±0.27，与模型组比较差异均有统计学意义（P＜0.05或P＜0.01）。结论芹菜素可不同程度的拮抗LPS引起的小鼠ALI，以中剂量组改善效果最好，其保护作用可能与抑制p38MAPK信号通路活化、减少TNF-α和ICAM-1等炎症因子表达有关。
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