Disruption of the Cyp7b1 Gene in Rats Increases Secretion of Very Low Density Lipoproteins by Decreasing Low Density Lipoprotein Receptor on Plasma Membrane

In agreement with this, an increased hepatic secretion of VLDL in fasting rats treated with tyloxapol and absence of low-density receptor protein on the surface of hepatocytes were observed. The decrease in LDLr was not due to decreased mRNA expression but to increased expression of its protease Psck9. These data indicate that CYP7B1 and its metabolite 25-hydroxycholesterol modulates the metabolism of VLDL in liver by decreasing its capture by LDL receptor. These observations were partially recovered by exogenous plasmid hydrodinamic injection与此结论相符，研究观察到经泰洛沙泊（tyloxapol）处理的禁食大鼠肝脏分泌极低密度脂蛋白（VLDL）的水平显著升高，且肝细胞表面的低密度脂蛋白受体蛋白（low-density receptor protein）表达缺失。进一步分析显示，低密度脂蛋白受体（LDLr）的表达下调并非由其自身的mRNA表达水平降低所致，而是因其蛋白酶前蛋白转化酶枯草溶菌素9（Psck9）的表达上调所介导。上述实验数据表明，细胞色素P450 7B1（CYP7B1）及其代谢产物25-羟基胆固醇（25-hydroxycholesterol）可通过降低极低密度脂蛋白被低密度脂蛋白受体的摄取效率，从而调控肝脏内极低密度脂蛋白的代谢过程。经外性质粒流体动力学注射干预后，上述部分观测结果得到了恢复。