Rioux F, Perea A, Yousef I M, Lévy E, Malli L, Carrillo M C, Tuchweber B
Centre de Recherche Pediatrique Hospital Ste-Justine, Montreal, Quebec, Canada.
Biochim Biophys Acta. 1994 Sep 15;1214(2):193-202. doi: 10.1016/0005-2760(94)90044-2.
Earlier studies suggested that the secretory rate maximum (SRm) of bile acid and the cholestasis which occurs after the SRm is reached may be determined by the hepatic or extrahepatic biliary phospholipid pool. We therefore investigated whether bile formation and the bile acid SRm could be influenced by feeding a diet enriched in phospholipids. Male rats were fed phospholipid (PLD) or triacylglycerol (TgD)-enriched diet for 3 days, and bile formation as well as biliary lipid output were measured on the 4th day. In other similarly fed groups, cholic acid was infused in stepwise increasing doses to determine the effect of PLD on the SRm of cholic acid. The plasma lipid levels were significantly lower in PLD and TgD diets compared to basal diet. But, while the levels of total cholesterol (CH), HDL-CH, and phospholipid (PH) were not significantly altered by PLD compared to TgD, the triacylglycerol levels were markedly increased by PLD. In the liver of PLD fed rats, triacylglycerol and CH ester contents decreased by 39 and 62%, respectively, while free CH and PH contents were not significantly changed. The PLD significantly augmented spontaneous bile flow, bile acid, PH and CH secretion rates compared to TgD diet (65, 124, 164 and 654%, respectively). The enhanced biliary secretory function was associated with an increase in pericanalicular vacuoles and diverticuli in centrilobular hepatocytes. Compared to TgD fed rats, PLD rats showed a 2-fold decrease in the ratio of cholic acid/chenodeoxycholic acid in bile and a significant decrease in the % contribution of taurine conjugated BA. The PH fatty acids in bile were similar in both groups except that in PLD group the % contribution of C18:2 was higher than in TgD group. No differences were found in plasma membrane CH/PH content or total fatty acid composition. During bile acid infusion, the SRm and the total cholic acid secreted were significantly higher in the PLD than in the TgD rats. Moreover, the cholestatic response observed after high bile acid dose was markedly reduced by PLD. The results show that short-term feeding of PLD induces changes in CH and bile acid metabolism which result in enhanced biliary output of CH and PH. The enhanced pool of biliary lipid may protect plasma membranes from the deleterious effects of high bile acid concentrations.
早期研究表明,胆汁酸的最大分泌率(SRm)以及达到SRm后出现的胆汁淤积可能由肝内或肝外胆汁磷脂池决定。因此,我们研究了喂食富含磷脂的饮食是否会影响胆汁形成和胆汁酸SRm。雄性大鼠喂食富含磷脂(PLD)或三酰甘油(TgD)的饮食3天,并在第4天测量胆汁形成以及胆汁脂质输出。在其他同样喂食的组中,逐步增加剂量注入胆酸以确定PLD对胆酸SRm的影响。与基础饮食相比,PLD和TgD饮食组的血浆脂质水平显著降低。但是,与TgD相比,PLD组的总胆固醇(CH)、高密度脂蛋白胆固醇(HDL-CH)和磷脂(PH)水平没有显著变化,而PLD组的三酰甘油水平显著升高。在喂食PLD的大鼠肝脏中,三酰甘油和CH酯含量分别降低了39%和62%,而游离CH和PH含量没有显著变化。与TgD饮食相比,PLD显著增加了自发性胆汁流量、胆汁酸、PH和CH分泌率(分别为65%、124%、164%和654%)。胆汁分泌功能增强与中央小叶肝细胞胆小管周围空泡和憩室增加有关。与喂食TgD的大鼠相比,PLD大鼠胆汁中胆酸/鹅去氧胆酸的比例降低了2倍,牛磺酸结合型胆汁酸的贡献百分比显著降低。两组胆汁中的PH脂肪酸相似,只是PLD组中C18:2的贡献百分比高于TgD组。在质膜CH/PH含量或总脂肪酸组成方面未发现差异。在注入胆汁酸期间,PLD组的SRm和分泌的总胆酸显著高于TgD大鼠。此外,PLD显著降低了高胆汁酸剂量后观察到的胆汁淤积反应。结果表明,短期喂食PLD会引起CH和胆汁酸代谢变化,导致CH和PH的胆汁输出增加。胆汁脂质池的增加可能保护质膜免受高胆汁酸浓度的有害影响。