栀子苷对小鼠急性肺损伤保护机制的研究

Geniposide Protects against Lipopolysaccharide-induced Acute Lung Injury in Mice

为了探究栀子苷能否对脂多糖(LPS)致小鼠急性肺损伤发挥保护作用及其潜在的作用机制。雄性Balb/c小鼠,于鼻腔滴注LPS前1h腹腔注射栀子苷(50mg/kg)或者地塞米松注射液(5mg/kg),滴注LPS24h后,采用酶联免疫吸附法(ELISA)测定小鼠支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)、白介素(IL)-6和IL-10的浓度。通过细胞分类计数法分析BALF中细胞总数、巨噬细胞和中性粒细胞的变化。采用蛋白印迹法(Western-blot)分析核转录因子-κB(NF-κB)信号转导通路激活的程度。腹腔注射栀子苷可降低小鼠肺干湿比(W/D值);改善肺组织病理学结构,减少肺泡出血和炎性细胞浸润且伴有髓过氧化物酶活性下降;抑制促炎性细胞因子TNF-α和IL-6分泌,促进抗炎性细胞因子IL-10生成。栀子苷通过缓减炎症反应保护LPS致小鼠急性肺损伤,其机制可能与阻止NF-κB信号转导通路的激活有关。

The purpose of this study was to evaluate the effect of geniposide on acute lung injury （ALI） induced by lipopolysaceharide （LPS） in mice. Male BALB/e mice were pretreated with dexamethasone （DEX） or geniposide 1 h before intranasal instillation of LPS. Seven hours after LPS challenge, the levels of tumor necrosis faetor-α （TNF-α）, interleukin-6 （IL-6）, and interleukin-10 （IL-10） in the bronchoalveolar lavage fluid （BALF） were measured. The number of total cells, neutrophils, and maerophages in the BALF were also determined. The extent of IκB phosphorylation was detected by Western-blot. Pretreatment with geniposide was found to decrease the W/D ratio of the lung tissue; attenuate lung histopathologic changes, alveolar hemorrhage, and neutrophil infiltration, with evidence of reduced myeloperoxidase （MPO） activity; down-regulate the level of pro-inflammatory mediators, including TNF-α and IL-6; up-regulate the concentration of IL-10; and inhibit the phosphorylation of IκB. Taken together, our results suggested that Geniposide might provide protective effects against LPS-induced ALI by mitigating the inflammatory response and that the compound＇ s mechanism of action might involved blocking the nuclear faetor-kappaB （NF-κB） signaling pathway activation.