肝靶向胆酸-脂肪酸偶合物的研究进展

Research progress in liver targeted fatty acid bile acid conjugates

脂肪酸-胆酸结合物(FABACs)是由脂肪酸与胆酸通过酰胺键偶联形成的一类化合物.FABACs在体外能够增加胆汁中胆固醇的溶解度,抑制人工胆汁和天然胆汁中胆固醇的结晶;仓鼠和小鼠po给药后,FABACs能够预防由高脂饮食所致的胆结石,并且对已形成的胆固醇结石有溶解作用;在Wister大鼠、仓鼠和多种小鼠模型上,FABACs口服给药后能够预防由高脂饮食所致的脂肪肝;进一步的研究表明FABACs还能够预防高脂饮食所致的动脉粥样硬化;作用机制研究结果表明,FABACs对肝脏中的胆固醇合成有抑制作用,对HMGCoA活性有一定的降低作用,对CYP7A1活性有增强作用,这些作用抑制了胆固醇的合成,促进了胆固醇的代谢和排出.

Fatty acid bile acid conjugates（FABACs）are synthetic lipid molecules designed to solubilize biliary cholesterol.FABACs were shown to delay,reduce,or prevent cholesterol crystallization in vitro and ex vivo in model bile solutions and in human bile.FABACs have also been shown to prevent the formation of cholesterol gallstones and to dissolve preexisting gallstones in experimental animal models.In addition to the beneficial effect on gallstone disease,FABACs have been demonstrated to be able to prevent diet-induced fatty liver,reduce atherosclerosis in C57Bl6 mice and increase faecal bile salt and neutral sterol secretion.