中药莪术激活PXR及对大鼠肝细胞色素P450 3A的影响  

Traditional Chinese medicine Rhizoma curcumae activates PXR and affects cytochrome P450 3A in the rat liver

作　　者：邵敬伟[1] 董海燕[1] 王涛[1] 郭养浩[1] 

机构地区：[1]福州大学药物生物技术与工程研究所,福建福州350002

出　　处：《中国药理学通报》2008年第4期504-509,共6页Chinese Pharmacological Bulletin

基　　金：福建省教育厅资助项目(NoJB05020);福州大学校人才基金资助项目(NoHX2005-3)

摘　　要：目的考察莪术能否通过体外激活PXR调节细胞色素P4503A4(CYP3A4)的转录表达及对大鼠肝脏CYP3A在酶活性及mRNA表达的诱导作用。方法在HepG2细胞中,采用瞬时共转染报告基因实验研究莪术对PXR介导的CYP3A4的转录调节作用;在大鼠体内,采用紫外分光光度法和RT-PCR技术检测莪术对大鼠肝脏CYP450含量及CYP3A同工酶红霉素N-脱甲基酶(ERD)的活性和CYP3A基因mRNA表达的影响。结果在体外报告基因实验研究中,莪术提取物及其有效成分能不同程度的诱导CYP3A4的表达;在大鼠体内实验中,莪术提取物能够增加CYP450蛋白含量和CYP3A酶活性;在mRNA水平上,莪术提取物能够明显诱导CYP3A1及CYP3A2的基因表达。结论莪术提取物及其有效成分能够明显激活PXR并诱导CYP3A4的转录表达;莪术提取物对大鼠体内CYP3A的酶活性及mRNA表达均有明显诱导作用。Aim To investigate whether Rhizoma curcumae could induce pregnane X receptor（PXR）-mediated transcriptional expression of CYP3A4 and study the modulatory effects on the enzyme activity and mR-NA expression of CYP3A in the rat liver. Methods Transient cotransfection reporter gene assays were performed in HepG2 cells; the rat liver microsomal cytochrome P450 and CYP3A isoenzyme-erythromycin N-demethylase（ERD） activities were determined by UV chromatography ;the mRNA expression level of CYP3A was detected by reverse transcriptase-polymerase chain reaction （ RT-PCR ）. Results In vitro investigation showed Rhizoma curcumae and its four selected constituents could induce the CYP3A4 transcriptional expression by activating PXR. In vivo investigation showed the CYP450 content of liver microsomes and enzyme activity of CYP3A were markedly increased and induced by Rhizoma curcumae extract;at the mRNA level, the expression of CYP3A1 and CYP3A2 gene were markedly induced by Rhizoma curcumae extract. Conclusions Rhizoma curcumae and its four selected constituents could induce the expression of the CYP3A4 gene transcriptional expression through activating PXR;Rhizoma curcumae extract could increase and induce the enzyme activity and mRNA expression of CYP3A.

关 键 词：莪术 CYP3A PXR RT—PCR 

分 类 号：R-332[医药卫生] R282.71