ROS在LPS下调鼠胎盘pxr等基因表达中的作用  

Role of reactive oxygen species on lipopolysaccharide-induced downregulation of the expression of pregnane X receptor,cyp3a11 and mdr1a in mouse placenta

作　　者：陈远华[1] 徐德祥[1] 王剑萍[1] 孙美芳[1] 魏凌珍[1] 

机构地区：[1]安徽医科大学卫生毒理学系,安徽合肥230032

出　　处：《毒理学杂志》2006年第6期354-356,共3页Journal of Toxicology

基　　金：国家自然科学基金(30371667;30572223);安徽省自然科学基金(050430714)

摘　　要：目的研究活性氧（ROS）在细菌脂多糖（LPS）下调小鼠胎盘孕烷X受体（pxr）及其靶基因细胞色素P-450 3a11（cyp3a11）和多药耐药基因1a（mdr1a）表达中的作用。方法小鼠妊娠第17天分别注射不同剂量LPS（0．1-0．5mg／kg，ip）；LPS＋PBN组在注射LPS（0．2mg／kg，ip）前30min和后3h给予2-苯叔丁基硝酮（PBN）；LPS＋NAC组在注射LPS（0．2mg／kg，ip）前30min和后3h给予N-乙酰半胱氨酸（NAC）；对照组给予等容量生理盐水或PBN／NAC。孕鼠分别于LPS处理后6和12h处死。结果LPS显著下词小鼠胎盘pxr，cyp3a11和mdr1a mRNA表达，进一步研究发现，妊娠晚期给予LPS后，胎盘组织MDA水平明显升高且GSH含量显著降低。PBN和NAC处理显著抑制LPS对胎盘pxr，cyp3a11和mdr1a mRNA表达的下调作用，且显著对抗LPS引起的氧化应激。结论LPS下调小鼠胎盘pxr、cyp3a11和mdr1a mRNA表达；ROS至少部分参与了LPS对小鼠胎盘pxr、cyp3a11和mdr1a mRNA表达的下调作用。Objective To investigate the role of reactive oxygen species （ROS）on lipopolysaccharide （IPS）-induced downregnlation of the expression of pregnane X receptor （pxr） and its target gene cytochrome P450 3a11 （cyp3a11） and multidmg resistance 1a （mdr1a） in mouse placenta.Methods In LPS groups, pregnant mice were injected intraperitoneally with different doses of LPS （0.1 - 0.5 mg/kg） on gestafional day （gd） 17; In LPS ＋ PBN group, pregnant mice were injected with N-tert-butyl-α-phenylnitrone（PBN） at 30 rain before and at 3 h after LPS （0.2 mg/kg, ip） ; In LPS ＋ NAC group, pregnant mice were injected with N- cetylcysteine （NAC） at 30 min before and at 3 h after LIPS （0.2 mg/kg, ip） ; saline- or PBN/ NAC- treated pregnant mice served as controls, mice were sacrificed at 6 h or 12 h after LPS. Results LPS significantly decreased placental pxr, cyp3a11 and mdr1a mRNA levels in a dose-dependent manner. PBN and NAC pretreatment attenuated LPS-induced down-regulation of pregnane X receptor, cyp3a11 and mdr1a mRNA levels in mouse placenta. PBN and NAC pretreatment also inhibited LPS-initiated lipid peroxidation and GSH depletion in mouse placenta. Conclusion LPS down-regulates placental pxr, cyp3a11 and mdr1a mRNA expressions. ROS may be involved in LPS-induced down-regulation of pxr, cyp3a11 and mdr1a in mouse placenta.

关 键 词：细菌内毒素 孕烷X受体 细胞色素P:450 3a11 多药耐药基因1a 胎盘 

分 类 号：R994.1[医药卫生—毒理学]