肝脏表达的Niemann-Pick C1-Like 1调节小鼠的胆汁胆固醇浓度

Hepatic Niemann-Pick C1-Like 1 regulates biliary cholesterol concentration in mice

目的:探讨人(NPC1L1)在小鼠肝脏的过表达对胆汁胆固醇重吸收的影响。方法:通过杂交NPC1L1基因敲除小鼠(L1-KO)与肝脏过表达人的NPC1L1的转基因小鼠(L1-Tg),获得无小鼠自身NPC1L1基因表达、在肝脏过表达或不表达人NPC1L1基因的小鼠(L1-Tgliv+和L1-Tgliv-)。给予L1-Tgliv+小鼠(实验组)及L1-Tgliv-小鼠(对照组)含0.2%胆固醇的饮食并测定2组小鼠胆汁的脂质分泌、血浆的脂质水平和粪便核心固醇的分泌。结果:与L1-Tgliv-小鼠相比,L1-Tgliv+小鼠的胆汁胆固醇水平降低了90%,同时粪便核心固醇的分泌也降低了10%,而血浆总胆固醇、游离胆固醇和胆固醇酯水平分别升高了38.6%、47.6%和36.6%。结论:小鼠肝脏NPC1L1的过表达可提高肝脏对胆汁中胆固醇的重吸收。

Objective：The aim of this study is to determine the role of overexpressing human NPCI L1 in the liver on biliary cholesterol re-absorption in mice. Methods： The L1-Tg^liv＋ and L1-Tg^liv- mice were generated by crossing NPC1L1 deficient mice （L1-KO） with transgenic mice overexpressing human NPC1L1 in liver（L1-Tg）. After being fed 0.2 % cholesterol diet for three weeks, the concentrations of biliary lipids, plasma lipids and fecal neutral sterol were measured by enzymatic method or gas-liquid chromatograph. Result：Compared with L1-Tg^liv- mice, L1-Tg^liv＋ mice showed 90% decrease in biliary cholesterol, 38.6%, 47.6% and 36.6% increase in plasma total cholesterol, free cholesterol and cholesterol ester, respectively, and 10% decrease in fecal neutral sterol. Conclusion： Overexpressing human NPC1L1 in the liver regulates biliary cholesterol re-absorption in mice.