Rokkas T, Vaja S, Murphy G M, Dowling R H
Division of Medicine, UMDS of Guy's Hospital, London, UK.
Digestion. 1990;46 Suppl 2:447-57. doi: 10.1159/000200420.
The aim of this study was to assess the effect inhibiting diamine oxidase (DAO) activity on intestinal adaptation after 80% proximal small bowel resection in the rat. Aminoguanidine (AG), a DAO inhibitor, was administered subcutaneously (25 mg kg-1 day-1) to rats for 11 days after small bowel transection (n = 6) or resection (n = 6). Two additional groups of animals (n = 6) served as transection or resection controls and received normal saline subcutaneously for the same period. On day 12 after operation, the animals were sacrificed, mucosal homogenates prepared from the ileal remnants (or from the control ileum), analysed for DAO and ornithine decarboxylase (ODC) activities, and the concentrations of the polyamines putrescine, spermidine, spermine, and the indices of mucosal mass (wet weight, protein and DNA) measured. The results were expressed both per unit length intestine and per milligram mucosal DNA. AG treatment completely inhibited DAO activity in both the transection control and resected rats. In the AG-treated resection group, inhibition of DAO activity was accompanied by increases (p less than 0.005) in all three indices of mucosal mass (wet weight, protein and DNA per centimetre intestine), putrescine concentrations (p less than 0.05) and ODC activity per centimetre intestine (p less than 0.001) when compared with the saline-treated resection controls. The results of this study suggest that inhibition of the putrescine-degrading enzyme, DAO, enhances the adaptive response to intestinal resection. Therefore, DAO may play a major role in regulating adaptive intestinal mucosal growth. Furthermore, inhibition of DAO activity could be important therapeutically in patients with the short bowel syndrome.
本研究旨在评估抑制二胺氧化酶（DAO）活性对大鼠80%近端小肠切除术后肠道适应性的影响。在小肠横断（n = 6）或切除（n = 6）后，给大鼠皮下注射DAO抑制剂氨基胍（AG，25 mg·kg⁻¹·d⁻¹），持续11天。另外两组动物（n = 6）作为横断或切除对照组，同期皮下注射生理盐水。术后第12天，处死动物，制备回肠残余组织（或对照回肠）的黏膜匀浆，分析DAO和鸟氨酸脱羧酶（ODC）活性，并测定多胺腐胺、亚精胺、精胺的浓度以及黏膜质量指标（湿重、蛋白质和DNA）。结果以每单位长度肠道和每毫克黏膜DNA表示。AG处理完全抑制了横断对照组和切除大鼠的DAO活性。与生理盐水处理的切除对照组相比，AG处理的切除组中，DAO活性的抑制伴随着黏膜质量的所有三个指标（每厘米肠道的湿重、蛋白质和DNA）、腐胺浓度（p < 0.05）以及每厘米肠道的ODC活性（p < 0.001）的增加（p < 0.005）。本研究结果表明，抑制腐胺降解酶DAO可增强对肠道切除的适应性反应。因此，DAO可能在调节适应性肠黏膜生长中起主要作用。此外，抑制DAO活性在短肠综合征患者的治疗中可能具有重要意义。
