补骨脂素与异补骨脂素对雌雄小鼠肝脏CYP450、UGT、SULT酶mRNA的影响  

Effects of psoralen and isopsoralen on mRNA of CYP450s,UGTs and SULTs in female and male mice

作　　者：孟昭君 王昭昕 翟玉霞 张玥[1,2] 周昆 MENG Zhao-jun;WANG Zhao-xin;ZHAI Yu-xia;ZHANG Yue;ZHOU Kun(Institute of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin,301617,China;State Key Laboratory of Component Traditional Chinese Medicine,Tianjin,301617,China)

机构地区：[1]天津中医药大学中医药研究院,天津301617 [2]组分中药国家重点实验室,天津301617

出　　处：《时珍国医国药》2023年第6期1329-1333,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家科技重大专项“重大新药创制”(2014ZX09304307-001-005);国家自然科学基金(81673826)。

摘　　要：目的探究补骨脂素和异补骨脂素给药对小鼠肝脏CYP450、UGT、SULT酶mRNA水平的影响。方法使用不同浓度补骨脂素及异补骨脂素给雌、雄ICR小鼠连续灌胃14d,提取小鼠肝脏中总RNA,Realtime-PCR法测定肝脏中CYP1A1,CYP2A4,CYP2C29,CYP2D9,CYP2E1,CYP3A11,UGT1A1,UGT1A6,UGT1A9及SULT1A1的mRNA转录水平。结果与对照组相比,雌鼠补骨脂素80mg/kg剂量组CYP2C29 mRNA表达显著上调,160mg/kg剂量组CYP2A4、CYP2C29、UGT1A6 mRNA表达显著上调,而雄鼠20mg/kg剂量组CYP3A11、UGT1A1、UGT1A6,40mg/kg剂量组CYP2C29、UGT1A6 mRNA表达显著上调,80mg/kg剂量组CYP2A4,160mg/kg剂量组CYP1A1、CYP2A4、CYP2C29 mRNA水平显著上调;雌鼠异补骨脂素20mg/kg剂量组CYP1A1 mRNA显著下调,40mg/kg剂量组CYP1A1、CYP2A4、CYP2C29、UGT1A1、UGT1A6、UGT1A9 mRNA显著上调,而雄鼠40mg/kg剂量组CYP2A4 mRNA显著上调,UGT、SULT酶未见明显差异。结论补骨脂素与异补骨脂素灌胃给药均可影响小鼠肝脏中药物代谢酶的mRNA转录水平,且雌雄动物变化存在一定差异。Objective To study the effects of psoralen and isopsoralen on mRNA expressions of CYP450s,UGTs and SULTs in mouse liver.Methods Female and male ICR mouse were gavaged with different concentrations of psoralen and isopsoralen for 14 consecutive days.Total RNA was extracted from the mouse liver,and the mRNA transcript levels of CYP1A1,CYP2A4,CYP2C29,CYP2D9,CYP2E1,CYP3A11,UGT1A1,UGT1A6,UGT1A9 and SULT1A1 were measured by Realtime-PCR.Results Compared with the control group,the mRNA expression of CYP2C29 was significantly up-regulated in the female psor-alen 80 mg/kg group,the mRNA expression of CYP2A4,CYP2C29 and UGT1A6 was significantly up-regulated in the female psoralen 160 mg/kg group;while the mRNA expression of CYP3A11,UGT1A1 and UGT1A6 was significantly up-regulated in the male psoralen 20 mg/kg group,the mRNA expression of CYP2C29 and UGT1A6 was significantly up-regulated in the male psoralen 40 mg/kg group,the mRNA expression of in the CYP2A4 was significantly up-regulated in the male psoralen 80 mg/kg group,and the mRNA expression of CYP1A1,CYP2A4 and CYP2C29 was significantly up-regulated in the male psoralen 160 mg/kg group.Compared with the control group,the mRNA expression of CYP1A1 was significantly down-regulated in the female isopsoralen 20mg/kg group,and the mRNA expression of CYP1A1,CYP2A4,CYP2C29,UGT1A1,UGT1A6 and UGT1A9 was significantly up regulated in the female isopsoralen 40mg/kg group,while the mRNA expression of CYP2A4 was significantly up-regulated in the male isopsoralen 40mg/kg group,and there was no significant difference in UGTs and SULTs in the male isopsor-alen group.Conclusion Psoralen and isopsoralen can affect the mRNA expression of drug metabolic enzymes in mouse liver,and there are some differences between male and female animals.

关 键 词：补骨脂素 异补骨脂素 CYP450 UGT SULT MRNA 雌雄差异 

分 类 号：R285.5[医药卫生—中药学]