Wächter S, Krähenbühl L, Schäfer M, Krähenbühl S
Department of Clinical Pharmacology, University Hospital, Berne, Switzerland.
J Hepatol. 1999 Feb;30(2):242-8. doi: 10.1016/s0168-8278(99)80069-5.
BACKGROUND/AIMS: Rats with long-term bile duct ligation (BDL rats) have impaired hepatic fatty acid metabolism and alterations in carnitine homeostasis. Analysis of the carnitine tissue and body fluid pools was used as a tool to study hepatic fatty acid metabolism in BDL rats and after reversal of bile duct ligation by Roux-en-Y anastomosis for 5 (RY5) or 14 days (RY14)
Control rats were pair-fed to treated rats, and all rats were studied after starvation for 24 h. Carnitine was analyzed by a radioenzymatic method and by high performance liquid chromatography.
Both BDL and RY rats had decreased plasma beta-hydroxybutyrate concentrations, whereas free fatty acid plasma concentrations were not different from control rats. Free carnitine plasma concentrations were not different between BDL or RY and control rats, whereas acetylcarnitine concentrations were decreased in BDL and RY rats, and showed a positive correlation with the plasma beta-hydroxybutyrate concentrations. In comparison to control rats, the total hepatic carnitine content was increased in BDL and RY rats, both when expressed per g tissue and per total liver. This rise in the hepatic carnitine content was due to increases in both free and acylcarnitines, including acetylcarnitine. In comparison to control rats, the hepatic concentration of beta-hydroxybutyrate was decreased in BDL and RY rats, findings compatible with impaired formation of ketone bodies from acetyl-CoA. Urinary excretion of total carnitine was not different between treated and control rats.
Hepatic metabolism of fatty acids is impaired in BDL rats and does not recover during the 14 days after Roux-en-Y anastomosis. The increased hepatic carnitine content in BDL and RY rats can best be explained by decreased export of carnitine from the hepatocytes. The alterations in the hepatic carnitine pool and impaired hepatic fatty acid metabolism in BDL and RY rats are compatible with impaired ketogenesis.
背景/目的：长期胆管结扎的大鼠（BDL大鼠）存在肝脏脂肪酸代谢受损及肉碱稳态改变。分析肉碱组织和体液库作为研究BDL大鼠以及经Roux - Y吻合术胆管结扎逆转5天（RY5）或14天（RY14）后肝脏脂肪酸代谢的工具。
对照大鼠与处理大鼠进行配对喂养，所有大鼠在饥饿24小时后进行研究。肉碱通过放射酶法和高效液相色谱法进行分析。
BDL大鼠和RY大鼠的血浆β-羟基丁酸浓度均降低，而游离脂肪酸血浆浓度与对照大鼠无差异。BDL大鼠、RY大鼠与对照大鼠之间的游离肉碱血浆浓度无差异，而BDL大鼠和RY大鼠的乙酰肉碱浓度降低，且与血浆β-羟基丁酸浓度呈正相关。与对照大鼠相比，BDL大鼠和RY大鼠的肝脏总肉碱含量增加，无论是以每克组织还是以整个肝脏计算。肝脏肉碱含量的增加是由于游离和酰基肉碱（包括乙酰肉碱）均增加。与对照大鼠相比，BDL大鼠和RY大鼠的肝脏β-羟基丁酸浓度降低，这一结果与由乙酰辅酶A生成酮体的过程受损相符。处理大鼠与对照大鼠的总肉碱尿排泄量无差异。
BDL大鼠的肝脏脂肪酸代谢受损，且在Roux - Y吻合术后14天内未恢复。BDL大鼠和RY大鼠肝脏肉碱含量增加的最佳解释是肝细胞肉碱输出减少。BDL大鼠和RY大鼠肝脏肉碱库的改变及肝脏脂肪酸代谢受损与酮体生成受损相符。
