【摘要】 目的研究D-双功能蛋白(DBP)活性增加对胆汁酸合成的影响,从整体水平上探讨DBP在胆汁酸合成中的作用。方法将20只雄性Wistar大鼠随机分为邻苯二甲酸二异辛酯(DEHP)组(n=10)和对照组(n=10)。分别测定两组大鼠血清甘油三酯和总胆固醇的变化,肝脏过氧化物酶体增殖剂激活受体α(PPARα)、DBP和胆固醇7α-羟化酶(CYP7A1)mRNA的变化,以及DBP活性和粪中胆汁酸含量。结果与对照组相比,DEHP组大鼠血清甘油三酯明显降低(P<0.01),肝脏PPARαmRNA表达明显增加(P<0.01)。在DBPmRNA表达及活性升高(P<0.01)的同时,CYP7A1mRNA表达加强,是对照组的1.6倍(P<0.01);粪中胆汁酸排出增加,是对照组的1.9倍(P<0.01)。DBPmRNA水平及其活性与CYP7A1mRNA水平均呈明显的正相关(r=0.89,P<0.01;r=0.95,P<0.01)。结论DBPmRNA表达及活性的升高,可引起CYP7A1表达及胆汁酸合成增加,DBP协同CYP7A1参与胆汁酸的生物合成。更多还原

【Abstract】 Objective To determine the physiological role of D-bifunctional protein(DBP)in bile acid biosynthesis through investigating the effect of increasing activity of DBP on bile acid biosynthesis. Methods Twenty male Wistar rats were divided into two groups: diethylhexyl phthalate(DEHP)group (n = 10)and control group(n = 10). Serum triglyceride, total cholesterol, hepatic DBP activity, and fecal bile acids were assayed. The mRNA levels of hepatic peroxisome proliferator-activated receptor α(PPARα), DBP, and cholesterol 7α-hydroxylase(CYP7A1)were detected by RT-PCR. Results Compared with control group, serum triglyceride level was decreased significantly and PPARαmRNA level was increased significantly in DEHP group(P < 0.01). Together with a sharp induction of DBP mRNA expression and DBP activity in DEHP group(P < 0.01), the levels of CYP7A1 mRNA and fecal bile acids were significantly increased by 1.9 times and 1.6 times respectively compared to control group(P < 0.01). There was a significantly positive correlation between DBP mRNA level or DBP activity and CYP7A1 mRNA level(r = 0.89, P < 0.01; r = 0.95, P < 0.01). Conclusion The up-regulation of DBP mRNA and activity in liver can result in the increase in CYP7A1 mRNA expression and bile acid biosynthesis, suggesting that DBP may be involved in bile acid biosynthesis together with CYP7A1.更多还原