胆汁成分和物理化学性质在奥曲肽相关胆囊结石发病机制中的作用

The role of bile composition and physical chemistry in the pathogenesis of octreotide-associated gallbladder stones.

作者信息

Hussaini S H, Murphy G M, Kennedy C, Besser G M, Wass J A, Dowling R H

机构信息

Gastroenterology Unit, Guy's Hospital, London, England.

出版信息

Gastroenterology. 1994 Nov;107(5):1503-13. doi: 10.1016/0016-5085(94)90556-8.

DOI:10.1016/0016-5085(94)90556-8

PMID:7926514

Abstract

BACKGROUND/AIMS: Treatment of acromegaly with octreotide inhibits cholecystokinin release and gallbladder contraction and induces gallbladder stones. However, little is known about the effects of octreotide on bile composition.

METHODS

Fresh gallbladder bile was obtained from three groups: (1) 11 nonacromegalic patients with cholesterol gallstones, (2) 6 acromegalic patients with octreotide-associated stones (treatment, 300-600 micrograms/day for 3-66 months), and (3) 8 acromogalic patients with no stones before octreotide treatment, 5 of whom were reexamined after 3-24 months of therapy.

RESULTS

Compared with stone-free acromegalic patients untreated with octreotide, bile from patients with cholesterol stones and from acromegalic patients with octreotide-associated stones had greater saturation indices (mean +/- SEM) (1.52 +/- 0.17 and 1.32 +/- 0.14 vs. 0.90 +/- 0.05, respectively; P < 0.01); more cholesterol in vesicles (61.2% +/- 4.5% and 67.7% +/- 7.2% vs. 37.7% +/- 3.5%; P < 0.009); more unstable vesicles (cholesterol/phospholipid ratios, 0.97 +/- 0.12 and 0.81 +/- 0.16 vs. 0.52 +/- 0.05; P < 0.02); more rapid nucleation (< 5 and < 5 days vs. > 18 days; P < 0.003); and more deoxycholic acid (22.8% +/- 2.4% and 23.6% +/- 4.8% vs. 13.9% +/- 1.4%; P < 0.05). In the paired studies, the saturation indices increased from 0.89 +/- 0.07 before octreotide treatment to 1.12 +/- 0.03 during octreotide treatment (P < 0.02), as did the percentage of deoxycholic acid from 13.3% +/- 2.1% to 24.9% +/- 2.7% (P < 0.03).

CONCLUSIONS

Acromegalic patients with octreotide-associated gallstones and stone-free acromegalic patients treated with octreotide have similar changes in bile composition to those in patients with "conventional" cholesterol gallstone disease.

摘要

背景/目的：用奥曲肽治疗肢端肥大症会抑制胆囊收缩素的释放和胆囊收缩，并诱发胆结石。然而，关于奥曲肽对胆汁成分的影响却知之甚少。

方法

从三组患者中获取新鲜胆囊胆汁：（1）11例患有胆固醇结石的非肢端肥大症患者；（2）6例患有与奥曲肽相关结石的肢端肥大症患者（治疗剂量为300 - 600微克/天，疗程3 - 66个月）；（3）8例在接受奥曲肽治疗前无结石的肢端肥大症患者，其中5例在治疗3 - 24个月后接受复查。

结果

与未接受奥曲肽治疗的无结石肢端肥大症患者相比，患有胆固醇结石的患者以及患有与奥曲肽相关结石的肢端肥大症患者的胆汁具有更高的饱和指数（均值±标准误）（分别为1.52±0.17和1.32±0.14，对比0.90±0.05；P < 0.01）；囊泡中胆固醇含量更高（分别为61.2%±4.5%和67.7%±7.2%，对比37.7%±3.5%；P < 0.009）；不稳定囊泡更多（胆固醇/磷脂比率分别为0.97±0.12和0.81±0.16，对比0.52±0.05；P < 0.02）；成核更快（分别< 5天和< 5天，对比> 18天；P < 0.003）；脱氧胆酸更多（分别为22.8%±2.4%和23.6%±4.8%，对比13.9%±1.4%；P < 0.05）。在配对研究中，饱和指数从奥曲肽治疗前的0.89±0.07增加至治疗期间的1.12±0.03（P < 0.02），脱氧胆酸百分比也从13.3%±2.1%增加至24.9%±2.7%（P < 0.03）。