Carulli N, Ponz De Leon M, Zironi F, Pinetti A, Smerieri A, Iori R, Loria P
J Lipid Res. 1980 Jan;21(1):35-43.
The activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and 7alpha-hydroxylase, the enzymes controlling the rate of hepatic synthesis, respectively, of cholesterol and bile acids, and the microsomal cholesterol content were evaluated in 25 patients with cholesterol gallstones and 17 subjects without gallstones. The same quantities were estimated in 16 additional patients with gallstones given chenodeoxycholic (CDCA) or ursodeoxycholic acid (UDCA) at a dose of 15 mg/kg per day in order to investigate the comparative effect of a short term (7 days) administration of the two bile acids on the hepatic sterol metabolism. As compared to the controls, subjects with gallstones exhibited a 36% decrease of 7alpha-hydroxylase (26.8 +/- 6.2 versus 41.7 +/- 4.2 pmol/min per mg protein) and a 24% increase of the microsomal cholesterol (78.7 +/- 15.3 versus 63.1 +/- 18.1 nmol/mg protein). Although higher in the gallstone patients, the activity of HMG-CoA reductase did not differ significantly in the two groups of subjects. Administration of CDCA and UDCA changed the bile acid pool composition so that the fed bile acid predominated in the bile (mean CDCA 73% and mean UDCA 54%). Bile lipid composition did not appreciably change. In the eight subjects treated with CDCA the activity of HMG-CoA reductase was reduced to 45% of the value of untreated subjects (27.9 +/- 14.5 versus 63.5 +/- 25.3 pmol/min per mg protein) whereas in the eight subjects treated with UDCA the same enzyme showed a twofold increase (123.5 +/- 20.9). In the treated groups 7alpha-hydroxylase activity was somewhat decreased but the values did not differ significantly from those of the untreated subjects. Microsomal cholesterol content decreased with CDCA (64.8 +/- 11.6 nmol/mg protein) as well as with UDCA (59.1 +/- 10.1) treatment; however in the latter the difference attained statistical significance (P < 0.05). Altogether the results would suggest that in the liver of patients with gallstones the conversion of cholesterol to bile acids is somewhat reduced, and that changing the bile acid pool composition, by exogenous bile acid feeding, has disparate effects on hepatic cholesterol synthesis. The findings could represent the acute changes produced by bile acid feeding, however they could imply that the effects of two bile acids in dissolving cholesterol gallstones might not be related only to the changes in hepatic sterol metabolism.-Carulli, N., M. Ponz De Leon, F. Zironi, A. Pinetti, A. Smerieri, R. Iori, and P. Loria. Hepatic cholesterol and bile acid metabolism in subjects with gallstones: comparative effects of short term feeding of chenodeoxycholic and ursodeoxycholic acid.
在25例胆固醇结石患者和17例无结石受试者中，分别评估了3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶和7α-羟化酶的活性，这两种酶分别控制肝脏中胆固醇和胆汁酸的合成速率，同时还评估了微粒体胆固醇含量。另外16例结石患者接受了剂量为每天15mg/kg的鹅去氧胆酸（CDCA）或熊去氧胆酸（UDCA）治疗，以研究短期（7天）给予这两种胆汁酸对肝脏固醇代谢的比较效果。与对照组相比，结石患者的7α-羟化酶活性降低了36%（26.8±6.2对41.7±4.2pmol/min per mg蛋白），微粒体胆固醇增加了24%（78.7±15.3对63.1±18.1nmol/mg蛋白）。尽管结石患者的HMG-CoA还原酶活性较高，但两组受试者之间没有显著差异。给予CDCA和UDCA改变了胆汁酸池组成，使得进食后的胆汁酸在胆汁中占主导（平均CDCA为73%，平均UDCA为54%）。胆汁脂质组成没有明显变化。在接受CDCA治疗的8例受试者中，HMG-CoA还原酶活性降至未治疗受试者的45%（27.9±14.5对63.5±25.3pmol/min per mg蛋白），而在接受UDCA治疗的8例受试者中，该酶活性增加了两倍（123.5±20.9）。在治疗组中，7α-羟化酶活性有所降低，但与未治疗受试者的值没有显著差异。微粒体胆固醇含量在CDCA治疗后降低（64.8±11.6nmol/mg蛋白），在UDCA治疗后也降低（59.1±10.1）；然而，后者的差异具有统计学意义（P<0.05）。总体而言，结果表明，在结石患者的肝脏中，胆固醇向胆汁酸的转化有所减少，通过外源性胆汁酸喂养改变胆汁酸池组成，对肝脏胆固醇合成有不同的影响。这些发现可能代表了胆汁酸喂养产生的急性变化，然而它们可能意味着两种胆汁酸溶解胆固醇结石的作用可能不仅仅与肝脏固醇代谢的变化有关。-卡鲁利，N.，M.庞兹·德莱昂，F.齐罗尼，A.皮内蒂，A.斯梅里耶里，R.约里，和P.洛里亚。结石患者肝脏胆固醇和胆汁酸代谢：短期给予鹅去氧胆酸和熊去氧胆酸的比较效果。
