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肝硬化患者外周和内脏吲哚和异吲哚水平:肝性脑病病理生理学研究。

Peripheral and splanchnic indole and oxindole levels in cirrhotic patients: a study on the pathophysiology of hepatic encephalopathy.

机构信息

Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.

出版信息

Am J Gastroenterol. 2010 Jun;105(6):1374-81. doi: 10.1038/ajg.2009.738. Epub 2010 Feb 2.

DOI:10.1038/ajg.2009.738
PMID:20125128
Abstract

OBJECTIVES

Intestinal bacteria metabolize tryptophan into indole, which is then further metabolized into oxindole, a sedative compound putatively involved in the pathophysiology of hepatic encephalopathy (HE). The aim of this study was to measure indole and oxindole levels in patients with cirrhosis with or without HE and to establish whether an intestinal production and a hepatic metabolism of these substances exist.

METHODS

We studied 10 healthy subjects (controls) and 51 cirrhotic patients: 17 without HE, 14 with a minimal HE, 8 with overt HE, and 12 who had undergone a transjugular intrahepatic portosystemic shunt (TIPS) procedure. In the last group, blood was collected from the artery, and the portal and hepatic veins during TIPS construction and from the peripheral veins before, immediately after, and at weekly intervals during the first month after TIPS.

RESULTS

Plasma indole levels were significantly higher in patients with overt HE. Oxindole levels were higher in cirrhotics than in controls. Indole and ammonia were significantly correlated (r=0.66). Peripheral and splanchnic determinations showed that indole was produced in the intestine and cleared by the liver, similar to ammonia. TIPS implantation increased both indole and ammonia levels. After TIPS, the psychometric performance worsened in 4 of the 12 patients. The increase in indole plasma concentrations in these four patients was higher than in those who remained stable after undergoing TIPS.

CONCLUSIONS

Indole correlates with HE and has a significant intestinal production and hepatic extraction; its level increases after TIPS and is related to psychometric performance. These data suggest that indole may be involved in the pathophysiology of HE.

摘要

目的

肠道细菌将色氨酸代谢为吲哚,吲哚进一步代谢为氧吲哚,氧吲哚是一种镇静化合物,推测与肝性脑病(HE)的病理生理学有关。本研究旨在测量有或无 HE 的肝硬化患者的吲哚和氧吲哚水平,并确定这些物质是否存在肠道产生和肝脏代谢。

方法

我们研究了 10 名健康受试者(对照组)和 51 名肝硬化患者:17 名无 HE,14 名轻度 HE,8 名显性 HE,12 名接受经颈静脉肝内门体分流术(TIPS)治疗。在后一组中,在 TIPS 构建过程中从动脉、门静脉和肝静脉以及 TIPS 后第 1 个月内每周从外周静脉采集血液。

结果

显性 HE 患者的血浆吲哚水平显著升高。肝硬化患者的氧吲哚水平高于对照组。吲哚和氨之间存在显著相关性(r=0.66)。外周和内脏测定表明,吲哚在肠道中产生并被肝脏清除,类似于氨。TIPS 植入后,吲哚和氨的水平均升高。在 12 名患者中,有 4 名患者的心理测量表现恶化。这 4 名患者的吲哚血浆浓度升高高于 TIPS 后保持稳定的患者。

结论

吲哚与 HE 相关,具有显著的肠道产生和肝脏提取;其水平在 TIPS 后增加,并与心理测量表现相关。这些数据表明,吲哚可能参与 HE 的病理生理学。

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