Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat
Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat
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DOI：
10.1152/ajpgi.00017.2008
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发表时间：
2008-04-01
影响因子：
4.5
通讯作者：
Vore, Mary
中科院分区：
文献类型：
--
作者：
Wooton-Kee, Clavia Ruth;Cohen, David E.;Vore, Mary
哺乳期大鼠胆汁酸池的大小和胆固醇7α羟基酶的表达增加。Am J Physiol胃肠病肝生理学294：G1009-G1016,2008。2008年2月21日首次出版；DOI：10.1152/ajpgi.00017.2008。-哺乳期肝脏和回肠的最大胆汁酸分泌率和胆汁酸转运体的表达增加，可能是为了促进胆汁酸的肠-肝再循环。我们测定了与雌性处女对照组相比，哺乳期大鼠胆汁酸池的大小和组成以及胆汁酸合成途径的关键酶[胆固醇7α-羟基酶(Cyp7a1)、固醇27-羟基酶(Cyp27a1)和固醇12α-羟基酶(Cyp8b1)]的变化。与对照组相比，产后10天、14天和19-23天的胆汁酸池增加了1.9到2.5倍。哺乳期胆酸增加1.5倍，鼠李酸减少14%至20%，显著增加疏水性指数。反之，肝脏胆汁酸浓度和小分子异二聚体配对mRNA在哺乳期无明显变化。光照后16h(10h)Cyp7a1mRNA表达增加2.8倍，第10天Cyp7a1蛋白表达和胆固醇7α-羟基酶活性显著增加，第14天继续升高，第21天降至对照水平。在PP后第10天，Cyp27a1基因表达总体下降，Cyp27a1蛋白表达下降20%，但Cyp8b1基因和蛋白表达无明显变化。Cyp7a1表达PP的增加为胆酸池的增加提供了机制。
Increased cholesterol 7 alpha-hydroxylase expression and size of the bile acid pool in the lactating rat. Am J Physiol Gastrointest Liver Physiol 294: G1009-G1016, 2008. First published February 21, 2008; doi:10.1152/ajpgi.00017.2008.- Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enterohepatic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway [ cholesterol 7 alpha-hydroxylase (Cyp7a1), sterol 27-hydroxylase (Cyp27a1), and sterol 12 alpha-hydroxylase (Cyp8b1)] in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold [ postpartum ( PP) days 10, 14, and 19-23], compared with controls. A 1.5-fold increase in cholic acids and a 14 to 20% decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and small heterodimer partner mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h ( 10 h of light) demonstrated a shift in the diurnal rhythm at day 10 PP; Cyp7a1 protein expression and cholesterol 7 alpha-hydroxylase activity were significantly increased at this time and remained elevated at day 14 PP but decreased to control levels by day 21 PP. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 PP. The increase in Cyp7a1 expression PP provides a mechanism for the increase in the bile acid pool.