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目的探讨乙醇和异戊基丙醇是否可以调节尿苷二磷酸葡萄糖醛酸基转移酶（ＵＧＴ）的表达来影响药物的代谢。方法应用大鼠动物模型和原始鼠肝细胞培养及Ｎｏｒｔｈｅｒｎ ｂｌｏｔ杂交技术，观察乙醇和异戊基丙醇处理肝细胞前后ＵＧＴ同工酶ｍＲＮＡ的变化。结果长期酒精喂养大鼠显著增加了ＵＧＴ１Ａ１ ｍＲＮＡ和ＵＧＴ１Ａ５ｍＲＮＡ的表达，分别为对照组的 １７７％和１６６％。长期酒精喂养同样也明显增加了ＵＧＴ２Ｂ１和ＵＧＴ２Ｂ３ ｍＲＮＡ的表达，分别为对照组的１７８％和１３２％。用乙醇和异戊基丙醇分别处理大鼠肝细胞后，均显著增加了ＵＧＴ１Ａ１，ＵＧＴ１Ａ５ＵＧＴ２Ｂ１和ＵＧＴ２Ｂ３ ｍＲＮＡ的表达，但ＵＧＴ１Ａ６ ｍＲＮＡ的表达未受影响。结论乙醇和异戊基丙醇可调节ＵＧＴ的表达，长期酒精摄入可干扰作为这些ＵＧＴ同工酶底物的内源性和外源性物质的代谢，特别是药物的代谢。
Objective To investigate whether ethanol and isopentyl alcohol can affect uridine diphosphate glucuronosyltransferase (UGT) expression to influence drug metabolism. Methods The changes of UGT isoenzymes mRNA in liver cells of ethanol and isopentyl alcohol were observed by using animal model of rat and primary hepatocytes culture and Northern blot hybridization. Results Long-term alcohol-fed rats significantly increased the expression of UGT1A1 mRNA and UGT1A5 mRNA, which were 177% and 166% of the control group, respectively. Long-term alcohol feeding also significantly increased UGT2B1 and UGT2B3 mRNA expression, 178% and 132%, respectively, of the control group. UGT1A1, UGT1A5UGT2B1 and UGT2B3 mRNA expression were significantly increased in rat hepatocytes treated with ethanol and isopentyl propanol, but the expression of UGT1A6 mRNA was not affected. CONCLUSION Ethanol and isopentylpropanol modulate the expression of UGT, a long-term alcohol intake that can interfere with the metabolism of endogenous and exogenous substances that serve as substrates for these UGT isozymes, particularly drug metabolism.