金雀异黄酮诱导HepG2细胞葡萄糖醛酸转移酶的表达-药理学(临床药理学)专业论文.docxVIP

ABSTRACTAIMS：Genistein(Gs)is ABSTRACT AIMS：Genistein(Gs)is a sort of phytoestrogen which has varied pharmacological functions．Scientists have found out that it Call modulate many drug—metabolizing enzymes through activating nuclear receptor． UDP-Glucuronyltransferase(UGT)is the most important phase II enzymes；it Call metabolize many endogenous and exogenous substances． 田1e alms of the study were to investigate the induction of expression of UGTlA．UGT2B and their isoforms in HepG2 cells by Ca and its possible mechanism． METHODS：We set up six expedmental groups，they are blank control，positive conlxol and four Gs group(1-lOpM)．Cells wegg collected at 12h．24h and 36h respectively after adlIlinistration．After extracting total RNA。we assayed the mRNA expression of PPARa。UGTlA and its isoforms UGTlAl and UGTlA9．UGT2B and its iosform UGT284 by semi-quantitative RT—PCR．After extracting microsomal protein,we assayed the protein expression of UGTlA bv Western Blot． RESU工TS：(1)Between 12—36h after adIIlinistration of the experimental dosages．Ca Can increase UGTlA and UGT2B mRNA expression slightly,there were no significant differences between blank and Gs groups．At 12h after administration．the levels of UGTlA and UGTlA9 mRNA were significantly increased in the Ca groups compared to吐lat in the blank(P0-05)；besides，UGTlA mRNA level correlated with Ca dosages positively(r=0．781，P=0．oD．At 24h，PPARa and UGT284 mRNA expression were significantly increased in the Ca groups in comparison with the blank．In addiction,P】M胁and UGT284 mRNA levels correlated with Gs dosages positively between 12-36h respectively． (2)nle UGTlA protein band intensity increased significantly treated with Gs for 24 h compared to control cells．(3)PPARa mRNA levels correlated witll UGT284 mRNA expression positively(r=O．568，PO．01)，while it didn’t show up between P】PARa mRNA and UGTlA9 mRNA． CONCLUTION：(1)1-IO．_M Gs can induce the expression of PPARa，UGT284，UGTlA and its isoform UGTlA9 significantly．These Ⅱ changes