【摘要】 目的研究肝X受体(LXR)和过氧化物酶体增殖剂激活受体α(PPARα)同时被激活对大鼠胆汁酸合成的影响。方法雄性SD大鼠分为对照组、血高胆固醇组(HC组)和血高胆固醇+非诺贝特组(HC+FENO组)。测定3组大鼠的总胆汁酸水平(血清和粪胆汁酸含量之和),RT-PCR方法检测肝过氧化物酶体棕榈酰CoA氧化酶(Acox1)、LXR、胆固醇7α-羟化酶(CYP7A1)、D-双功能蛋白(DBP)、三羟基粪甾烷酰CoA氧化酶(Acox2)、固醇12α-羟化酶(CYP8B1)和固醇27-羟化酶(CYP27A1)mRNA的表达水平。结果HC+FENO组的总胆汁酸水平显著高于HC组(P<0.01),且两组均显著高于对照组(P<0.01);对照组和HC组的Acox1和DBP mRNA水平差异无显著性,但均低于HC+FENO组(P<0.01);HC+FENO组和HC组的LXR和CYP7A1 mRNA水平差异无显著性,但均高于对照组(P<0.01,P<0.05);3组的Acox2、CYP8B1和CYP27A1 mRNA水平差异均无显著性。结论同时激活大鼠肝LXR和PPARα可上调CYP7A1和DBP mRNA的表达,通过经典途径增加胆汁酸的合成。更多还原

【Abstract】 Objective To explore the effects of the simultaneous activation of liver X receptor (LXR) and peroxisome proliferator-activated receptor α (PPARα) on bile acid biosynthesis in rats. Methods Totally 36 male SD rats were divided into three groups with 12 rats in each group: control group, high cholesterol (HC) group, and high cholesterol+fenofibrate (HC+FENO) group. Total bile acids (serum bile acids plus fecal bile acids) level was assayed. The levels of mRNA for peroxisomal palmitoyl-CoA oxidase (Acox1), LXR, cholesterol 7α-hydroxylase (CYP7A1), D-bifunctional protein (DBP), trihydroxycoprostanoyl-CoA oxidase (Acox2), sterol 12α-hydroxylase (CYP8B1), and sterol 27-hydroxylase (CYP27A1) in liver were detected by RT-PCR. Results Total bile acid level was significantly higher in HC+FENO group than in HC group (P<0.01), and both were significantly higher than that in control group (P<0.01). Compared with HC group, the mRNA expression of Acox1 and DBP was significantly higher in HC+FENO group (P< 0.01), but no statistical differences was found between HC group and control group. The mRNA levels of LXR and CYP7A1 in HC+FENO group and HC group were not significantly different but were both significantly higher than that in control group (P<0.01, P<0.05). No changes were observed in Acox2, CYP8B1, and CYP27A1 mRNA levels among these three groups. Conclusion Simultaneous activation of LXR and PPARα can increase of CYP7A1 and DBP mRNA expression and thus accelerates the biosynthesis of bile acid.更多还原