The transporter multidrug resistance protein 2 (MRP2) plays an important role in chronic pulmonary inflammation by transporting cigarette smoke and other related inflammatory mediators. However, it is not completely clear whether pulmonary inflammation caused by cigarette smoke extract (CSE) and lipopolysaccharide (LPS) is related to MRP2 and its signal factors. In this study, CSE combined with LPS was used to establish an inflammation model in vivo and in vitro. We found that compared with the control group, after CSE combined with LPS treatment, the expression of MRP2 in rat lung tissue in vivo and human alveolar cell line in vitro was down-regulated, while the expression of inflammatory factors was up-regulated. Through silencing and overexpression of FXR, it was found that silent FXR could down-regulate MRP2 and up-regulate the expression of inflammatory factors. On the contrary, overexpression of FXR could up-regulate MRP2 and down-regulate the expression of inflammatory factors. Our results show that CSE combined with LPS can down-regulate the expression of MRP2 under inflammatory conditions, and the down-regulation of MRP2 expression may be achieved partly through the FXR signal pathway.

转运蛋白多药耐药蛋白 2 (MRP2) 通过转运香烟烟雾和其他相关炎症介质在慢性肺部炎症中发挥重要作用。然而，由香烟烟雾提取物（CSE）和脂多糖（LPS）引起的肺部炎症是否与MRP2及其信号因子有关尚不完全清楚。本研究采用CSE联合LPS建立体内外炎症模型。我们发现，与对照组相比，CSE联合LPS治疗后，体内大鼠肺组织和体外人肺泡细胞系中MRP2的表达下调，而炎症因子的表达上调。通过 FXR 的沉默和过表达，发现沉默的FXR可以下调MRP2并上调炎症因子的表达。相反，FXR的过表达可以上调MRP2并下调炎症因子的表达。我们的研究结果表明，CSE 联合 LPS 可以下调炎症条件下 MRP2 的表达，并且 MRP2 表达的下调可能部分通过 FXR 信号通路实现。