双环醇对肝脏部分切除大鼠CYP450酶活性和表达的影响(英文)

Effects of bicyclol on the activity and expression of CYP450 enzymes of rats after partial hepatectomy

本研究考察双环醇对肝脏部分切除(PH)后大鼠肝脏微粒体细胞色素P450(CYP)活性、基因和蛋白表达的影响及相关机制。大鼠PH前灌胃给予双环醇(300 mg.kg-1)3次,PH后处死大鼠,取其血清和肝组织进行检测,依次测定血清谷丙转氨酶(ALT)、肝微粒体丙二醛(MDA)和肝脏总CYP含量、4种CYP同工酶活性、基因和蛋白表达。结果显示,双环醇可显著抑制PH大鼠血清ALT和肝微粒体MDA的升高,抑制肝脏总CYP含量的减少,抑制CYP2C6、2C11活性和mRNA表达的下降,明显抑制CYP3A1/2活性的下降,并上调CYP3A1和2E1的mRNA和蛋白表达。结果表明,双环醇对PH大鼠肝脏CYP450酶及部分同工酶活性和表达的改变有明显改善作用,其作用机制可能与其抗氧化作用和酶诱导作用密切相关。

The present study was performed to investigate the effect of bicyclol on hepatic microsomal cytochrome P450（CYP） activity,as well as gene and protein expressions in rats after partial hepatectomy（PH）.Bicyclol（300 mg·kg-1） was given to rats subjected to 70% hepatectomy three times before operation.At 6 and 48 h after PH,blood and liver tissue samples were collected for the measurement of serum alanine aminotransferase（ALT）,hepatic microsomal malondialdehyde（MDA） and total hepatic CYP content.The activities of four CYP isozymes were detected with liquid chromatography-mass spectrometry（LC-MS） and the gene and protein expressions were determined by RT-PCR and Western blotting assay.As a result,bicyclol pretreatment markedly inhibited the elevation of serum ALT and hepatic microsomal MDA,and prevented the decrease of total hepatic CYP content in PH rats.In addition,bicyclol significantly attenuated the reduction of CYP2C6 activity and mRNA expression,as well as the reduction of CYP2C11 activity in PH rats.Bicyclol can inhibit the decrease of CYP3A1/2 activity,and up-regulate the mRNA and protein expressions of CYP3A1 and CYP2E1.These results showed that bicyclol pretreatment might ameliorate abnormality in CYP450 isoforms during liver regeneration after PH,and this protective effect was likely due to its anti-oxidative property and enzyme induction.