四氯化碳诱导的肝硬化大鼠内脏内毒素水平

Splanchnic endotoxin levels in cirrhotic rats induced by carbon tetrachloride.

作者信息

Chu C J, Lee F Y, Wang S S, Chang F Y, Lin H C, Lu R H, Chan C C, Lee S D

机构信息

Department of Medicine, Taipei Veterans General Hospital, Taiwan, ROC.

出版信息

Zhonghua Yi Xue Za Zhi (Taipei). 2000 Mar;63(3):196-204.

PMID:10746415

Abstract

BACKGROUND

Bacterial translocation (passage of intestinal bacteria to mesenteric lymph nodes) observed in cirrhosis may be a source of endotoxin that can stimulate nitric oxide production and participate in the pathogenesis of hyperdynamic circulation. Currently, there are no published data concerning splanchnic endotoxin levels in cirrhotic rats. This study was designed to determine systemic and portal hemodynamics and to detect endotoxins in the portal and systemic circulation.

METHODS

Liver cirrhosis was induced by carbon tetrachloride intragastric gavage. Systemic and splanchnic endotoxin levels in control rats and cirrhotic rats with or without ascites were measured using a chromogenic Limulus assay. In addition, systemic and portal hemodynamic data were obtained using a thermodilution technique and catheterization.

RESULTS

Cirrhotic rats with ascites had the lowest systemic vascular resistance (2.6 +/- 0.1 mmHg.ml-1.min.100 g body weight, BW) compared with control rats (6.3 +/- 0.3 mmHg.ml-1.min.100 g BW; p < 0.05) and cirrhotic rats without ascites (3.7 +/- 0.3 mmHg.ml-1.min.100 g BW; p < 0.05). Cirrhotic rats with ascites displayed the highest splanchnic levels of endotoxin (10.6 +/- 3.1 pg/ml) compared with cirrhotic rats without ascites (2.0 +/- 0.7 pg/ml; p < 0.05) and control rats (2.0 +/- 0.4 pg/ml; p < 0.05). There was no difference in the splanchnic endotoxin levels between control rats and cirrhotic rats without ascites (p > 0.05). Similar results were observed with systemic endotoxin values (cirrhotic rats with ascites, 10.8 +/- 2.8 pg/ml; cirrhotic rats without ascites, 2.7 +/- 0.6 pg/ml; control rats, 2.5 +/- 0.4 pg/ml; p < 0.05). A significant correlation existed between portal and systemic endotoxin values in cirrhotic rats with or without ascites (r = 0.96, p < 0.001 and r = 0.9, p < 0.05, respectively), whereas this correlation did not exist in control rats (r = 0.5, p > 0.05).

CONCLUSIONS

Cirrhotic rats with ascites had the lowest systemic vascular resistance and the highest splanchnic endotoxin levels when compared with cirrhotic rats without ascites and control rats. These results suggest that splanchnic endotoxemia may be involved in the development and/or maintenance of hyperdynamic circulation.

摘要

背景

肝硬化患者中观察到的细菌移位（肠道细菌转移至肠系膜淋巴结）可能是内毒素的一个来源，内毒素可刺激一氧化氮生成并参与高动力循环的发病机制。目前，尚无关于肝硬化大鼠内脏内毒素水平的公开数据。本研究旨在测定全身和门静脉血流动力学，并检测门静脉和体循环中的内毒素。

方法

通过四氯化碳灌胃诱导肝硬化。使用显色鲎试剂法测量对照大鼠以及有或无腹水的肝硬化大鼠的全身和内脏内毒素水平。此外，采用热稀释技术和插管获取全身和门静脉血流动力学数据。

结果

与对照大鼠（6.3±0.3 mmHg·ml⁻¹·min·100 g体重，BW）和无腹水的肝硬化大鼠（3.7±0.3 mmHg·ml⁻¹·min·100 g BW；p<0.05）相比，有腹水的肝硬化大鼠全身血管阻力最低（2.6±0.1 mmHg·ml⁻¹·min·100 g体重，BW）。与无腹水的肝硬化大鼠（2.0±0.7 pg/ml；p<0.05）和对照大鼠（2.0±0.4 pg/ml；p<0.05）相比，有腹水的肝硬化大鼠内脏内毒素水平最高（10.6±3.1 pg/ml）。对照大鼠和无腹水的肝硬化大鼠之间内脏内毒素水平无差异（p>0.05）。全身内毒素值也有类似结果（有腹水的肝硬化大鼠，10.8±2.8 pg/ml；无腹水的肝硬化大鼠，2.7±0.6 pg/ml；对照大鼠，2.5±0.4 pg/ml；p<0.05）。有或无腹水的肝硬化大鼠门静脉和全身内毒素值之间存在显著相关性（分别为r = 0.96，p<0.001和r = 0.9，p<0.05），而对照大鼠中不存在这种相关性（r = 0.5，p>0.05）。