Pandak W M, Heuman D M, Hylemon P B, Chiang J Y, Vlahcevic Z R
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Gastroenterology. 1995 Feb;108(2):533-44. doi: 10.1016/0016-5085(95)90083-7.
BACKGROUND/AIMS: The decrease in cholesterol 7 alpha-hydroxylase induced by intraduodenal infusion of taurocholate in bile fistula rats may be indirect, i.e., mediated through release or absorption of an intestinal factor in response to the presence of bile salts in the intestine. The aim of this study was to determine if negative feedback regulation of cholesterol 7 alpha-hydroxylase can be shown when equimolar concentrations of taurocholate are administered intravenously, thus bypassing the intestine.
After 96 hours of biliary diversion, taurocholate (36 mumol.h-1.100 g, rat-1) was infused into the rats either intravenously or intraduodenally for the final 24 hours. Livers were then harvested for analysis of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase specific activity, cholesterol 7 alpha-hydroxylase specific activity, messenger RNA levels, and transcriptional activity.
Intraduodenally administered taurocholate significantly decreased HMG-CoA reductase and cholesterol 7 alpha-hydroxylase specific activity by more than 50% and cholesterol 7 alpha-hydroxylase steady-state messenger RNA levels and transcriptional activity by 50%-75%. In contrast, intravenous administration of taurocholate failed to down-regulate either cholesterol 7 alpha-hydroxylase or HMG-CoA reductase.
Passage of taurocholate through the intestine strongly potentiates negative feedback regulation of cholesterol 7 alpha-hydroxylase. A putative intestinal factor, released or absorbed in the presence of bile acids in the intestinal lumen, may play a role in the regulation of bile acid synthesis.
背景/目的：在胆瘘大鼠中，十二指肠内注入牛磺胆酸盐所诱导的胆固醇7α-羟化酶的降低可能是间接的，即通过对肠道中胆盐存在的反应，由一种肠因子的释放或吸收介导。本研究的目的是确定当静脉注射等摩尔浓度的牛磺胆酸盐从而绕过肠道时，是否能显示胆固醇7α-羟化酶的负反馈调节。
在胆汁引流96小时后，在最后24小时将牛磺胆酸盐（36μmol·h⁻¹·100g，大鼠⁻¹）静脉或十二指肠内注入大鼠。然后收获肝脏以分析3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶比活性、胆固醇7α-羟化酶比活性、信使核糖核酸水平和转录活性。
十二指肠内给予牛磺胆酸盐显著降低HMG-CoA还原酶和胆固醇7α-羟化酶比活性超过50%，并使胆固醇7α-羟化酶稳态信使核糖核酸水平和转录活性降低50%-75%。相比之下，静脉注射牛磺胆酸盐未能下调胆固醇7α-羟化酶或HMG-CoA还原酶。
牛磺胆酸盐通过肠道的过程强烈增强了胆固醇7α-羟化酶的负反馈调节。一种假定的肠因子，在肠腔内存在胆汁酸时释放或吸收，可能在胆汁酸合成的调节中起作用。
