LPS对小鼠肠上皮细胞孕烷X受体、维甲素X受体α和cyp3a11基因表达的下调作用  

Lipopolysaccharide down-regulates the expressions of pregnane X receptor, retinoid X receptor alpha and cytochrome P450 3a11 in mouse intestine

作　　者：张程[1] 徐德祥[1] 王剑萍[1] 孙美芳[1] 王华[1] 陈远华[1] 

机构地区：[1]安徽医科大学卫生毒理学系,合肥230032

出　　处：《安徽医科大学学报》2006年第5期487-490,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:30371667;30572223)

摘　　要：目的 研究细菌脂多糖（LPS）对小鼠肠上皮细胞孕烷x受体（PXR）、维甲素X受体α（RXRot）和cyp3a11的影响。方法该研究由2个实验组成：实验一，小鼠经腹腔注射给予不同剂量的LPS（0．1～5．0mg／kg），LPS注射后12h处死小鼠；实验二，小鼠用CYP3A诱导剂地塞米松（DEX，50mg／kg，ig）预处理3d，第4天，同时给予DEX（50mg／kg，ig）和LPS（1．0mg／kg，ip），LPS注射后24h处死小鼠。用RT-PCR技术检测肠上皮细胞的PXR、RXRot和cyp3a11 mRNA水平。用Nash法测定微粒体红霉素N脱甲基酶（ERND）的活性。结果LPS不仅抑制小鼠肠上皮细胞cyp3a11 mRNA表达，也显著下调小鼠肠上皮细胞PXR和RXRot mRNA的水平，并呈明显的剂量-效应关系。LPS显著抑制DEX对小鼠肠上皮细胞cyp3a11 mRNA表达和ERND活性的诱导作用。结论 LPS明显抑制小鼠肠上皮细胞cyp3a11表达；LPS对cyp3a11的下调作用与PXR和RXRot表达下降有关。Objective To investigate the effects of lipopolysaccharide （LPS） on the expressions of pregnane X receptor（PXR）, retinoid X receptor alpha （RXRa） and cyp3a11 in mouse intestine. Methods The present study included two separate experiments. In experiment I , a11 mice except controls received an intraperitoneal injection of LPS （0. 1 -5.0 mg/kg）. The mice were sacrificed at 12 h after LPS treatment. In experiment Ⅱ , a11 groups except control were administered with dexamethasone （ DEX, 50 mg/kg, ig） for 3 days. Then, on the fourth day, the mice were treated with DEX （50 mg/kg, ig） plus LPS （ 1.0 mg/kg, ip）. After that the mice were sacrificed at 24 h after LPS treatment. Intestinal PXR, RXRa and cyp3a11 mRNA were determined using reverse transcription polymerase chain reaction （RT-PCR）. Erythromycin N-demethylase （ERND） activities was measured using the method of the Nash reagent. Results LPS not only inhibited the expressions of intestinal cyp3a11, but also downregulated the levels of PXR and its heterodimer RXRa in a dose-dependent manner. Furthermore, LPS repressed the up-regulation of cyp3a11 mRNA and ERND catalytic activity in mice pretreated with PXR ligand DEX. Conclusion LPS suppresses the expressions of cyp3a11 in mouse intestine. LPS-induced down-regulation of cyp3al 1 is associated with inhibition of intestinal PXR and RXRa expressions.

关 键 词：脂多糖类/毒性 受体 类固醇 细胞色素P450酶系统 

分 类 号：R343.9[医药卫生—基础医学] R969.2