Ezetimibe and pemafibrate are lipid-lowering drugs and promote reverse cholesterol transport. However, it is unknown whether cholesterol is mainly excreted by hepatobiliary excretion or by non-biliary transintestinal cholesterol efflux (TICE). We evaluated the effects of ezetimibe and pemafibrate on hepatic and intestinal cholesterol transporter regulation in Sham-operated rats, and examined the effects of these drugs on TICE in bile duct-ligated rats. Seven-week-old male Sprague-Dawley rats were treated as follows for two weeks: 1) Sham, Sham operation; 2) BDL, bile duct ligation; 3) E-Sham, Sham + ezetimibe; 4) E-BDL, BDL + ezetimibe; 5) P-Sham, Sham + pemafibrate; and 6) P-BDL, BDL + pemafibrate. Blood, liver, jejunum, and feces were collected 72 h post-surgery. Hepatic cholesterol levels were decreased in P-Sham and E-Sham, and were lower in E-BDL and P-BDL than in BDL. Fecal cholesterol levels increased in E-Sham and P-Sham compared with Sham, and were higher in E-BDL and P-BDL than in BDL. In liver, Abcg5 mRNA showed induction in E-Sham, Abcg5 and Abca1 mRNA were induced in P-Sham, Abcg5 mRNA was reduced in E-BDL, and Abca1 mRNA was increased in P-BDL. In jejunum, Abcg5 mRNA was induced in E-Sham. Abcg8 mRNA was induced in E-Sham and P-Sham. NPC1L1 mRNA showed reduced expression in P-Sham and P-BDL. SR-B1 mRNA was reduced in P-Sham, and the expression decreased in P-BDL. LDL receptor mRNA was induced in BDL and P-BDL. Ezetimibe and pemafibrate may promote TICE by increasing Abcg5/g8, while pemafibrate may inhibit intestinal cholesterol absorption by decreasing SR-B1 and NPC1L1.

依折麦布和培马贝特是降脂药物，可促进胆固醇逆向转运。然而，尚不清楚胆固醇主要通过肝胆排泄还是通过非胆经肠胆固醇外流（TICE）排泄。我们评估了依折麦布和培马贝特对假手术大鼠肝和肠胆固醇转运蛋白调节的影响，并检查了这些药物对胆管结扎大鼠 TICE 的影响。七周龄雄性 Sprague-Dawley 大鼠按以下方式处理两周：1) 假手术，假手术；2) BDL、胆管结扎术；3) E-Sham、Sham + 依泽替米贝；4) E-BDL、BDL + 依折麦布；5) P-Sham、Sham + pemafibrate；和 6) P-BDL、BDL + pemafibrate。手术后 72 小时收集血液、肝脏、空肠和粪便。P-Sham 和 E-Sham 中的肝脏胆固醇水平降低，E-BDL 和 P-BDL 低于 BDL。与假手术相比，E-Sham 和 P-Sham 中的粪便胆固醇水平升高，并且 E-BDL 和 P-BDL 中的粪便胆固醇水平高于 BDL。在肝脏中，Abcg5 mRNA 在 E-Sham 中显示出诱导，Abcg5和Abca1 mRNA 在 P-Sham 中被诱导，Abcg5 mRNA 在E -BDL 中减少，而Abca1 mRNA 在 P-BDL 中增加。在空肠中，Abcg5 mRNA 在 E-Sham 中被诱导。Abcg8 mRNA 在 E-Sham 和 P-Sham 中被诱导。NPC1L1 mRNA 在 P-Sham 和 P-BDL 中的表达降低。P-Sham 中SR-B1 mRNA 减少，P-BDL 中表达减少。低密度脂蛋白受体mRNA 在 BDL 和 P-BDL 中被诱导。Ezetimibe 和 pemafibrate 可能通过增加 Abcg5/g8 来促进 TICE，而 pemafibrate 可能通过降低 SR-B1 和 NPC1L1 来抑制肠道胆固醇吸收。