志贺毒素对大鼠远端结肠中氯化钠转运的影响。

Effect of shiga toxin on NaCl transport in rat distal colon.

作者信息

Krishnan S, Ramakrishna B S, Keusch G T, Acheson D W, Pulimood A B, Mathan M

机构信息

Dept. of Gastrointestinal Sciences, Christian Medical College Hospital, Vellore, India.

出版信息

Scand J Gastroenterol. 1999 Aug;34(8):777-83. doi: 10.1080/003655299750025705.

DOI:10.1080/003655299750025705

PMID:10499478

Abstract

BACKGROUND

Shiga toxin causes net fluid secretion in rabbit jejunum by selectively targeting, and inhibiting protein synthesis in, absorptive villous cells. The effect of Shiga toxin on the colon, where it is presumably produced, is not known. This study was undertaken to investigate the effect of Shiga toxin on the rat distal colon.

METHODS

Net absorption of water and Na was determined by in vivo perfusion of closed loops of rat colon pre-exposed to Shiga toxin or saline. Unidirectional and net fluxes of 22Na and 36Cl were measured in vitro under voltage-clamp conditions across rat distal colon mucosa pre-exposed to Shiga toxin. Shiga toxin binding to sections of rat distal colon was localized by immunohistochemistry. Protein synthesis was measured in surface and crypt colonocytes with 3H-leucine incorporation.

RESULTS

In the in vivo perfusion studies net absorption of Na and water was increased in Shiga toxin-treated colon compared with controls (P < 0.01). In the studies carried out in vitro, J(net)Na and J9net)Cl across Shiga toxin-treated mucosa were found to be significantly higher than in control tissue (P < 0.001 and P < 0.01, respectively). Net absorption of Na or Cl did not increase further in the presence of 25 mM butyrate, indicating the absence of short-chain fatty acids (SCFA)-linked NaCl absorption in Shiga toxin-treated colon. Moreover, Shiga toxin-treated colon failed to respond to theophylline, which induced secretion in the normal colon. Immunohistochemistry showed Shiga toxin binding to crypt cells but not to surface cells in the distal colon. Shiga toxin inhibited protein synthesis (by 27.3%) in crypt cells but not in surface cells (P < 0.05).

CONCLUSIONS

An unexpected increase in water and NaCl absorption was noted in Shiga toxin-treated rat distal colon, which appears to result from selective effects of the toxin on secretory crypt cells.

摘要

背景

志贺毒素通过选择性靶向并抑制吸收性绒毛细胞中的蛋白质合成，导致兔空肠出现净液体分泌。志贺毒素对其可能产生的结肠的影响尚不清楚。本研究旨在探讨志贺毒素对大鼠远端结肠的影响。

方法

通过对预先暴露于志贺毒素或生理盐水的大鼠结肠闭合环进行体内灌注，测定水和钠的净吸收。在电压钳条件下，测量预先暴露于志贺毒素的大鼠远端结肠黏膜的22Na和36Cl的单向通量和净通量。通过免疫组织化学对志贺毒素与大鼠远端结肠切片的结合进行定位。用3H-亮氨酸掺入法测量表面和隐窝结肠细胞中的蛋白质合成。

结果

在体内灌注研究中，与对照组相比，志贺毒素处理的结肠中钠和水的净吸收增加（P < 0.01）。在体外研究中，发现通过志贺毒素处理的黏膜的J(net)Na和J9net)Cl显著高于对照组织（分别为P < 0.001和P < 0.01）。在存在25 mM丁酸盐的情况下，钠或氯的净吸收没有进一步增加，表明在志贺毒素处理的结肠中不存在短链脂肪酸（SCFA）相关的氯化钠吸收。此外，志贺毒素处理的结肠对茶碱无反应，而茶碱在正常结肠中可诱导分泌。免疫组织化学显示志贺毒素与远端结肠的隐窝细胞结合，但不与表面细胞结合。志贺毒素抑制隐窝细胞中的蛋白质合成（降低27.3%），但不抑制表面细胞中的蛋白质合成（P < 0.05）。