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吲哚美辛诱导的肠道炎症中白细胞与内皮细胞的黏附与粪便pH值相关。

Leucocyte endothelial cell adhesion in indomethacin induced intestinal inflammation is correlated with faecal pH.

作者信息

Arndt H, Palitzsch K D, Schölmerich J

机构信息

Department of Internal Medicine I, University of Regensburg, Germany.

出版信息

Gut. 1998 Mar;42(3):380-6. doi: 10.1136/gut.42.3.380.

Abstract

BACKGROUND

Recent studies indicate that faecal pH is acidified in patients with inflammatory bowel disease compared with healthy controls. In healthy volunteers, stool pH, faecal flora, and bile acid concentration could be affected by means of elemental diets.

AIMS

To assess the role of variations of faecal pH on leucocyte endothelial cell adhesion in indomethacin induced long lasting ileitis in rats.

METHODS

Indomethacin (7.5 mg/kg subcutaneously) was injected twice, 24 hours apart. Rats were either fed with the identical diet before and 10 days after the induction of inflammation until the experiment, or the diet was changed at the time of induction. Ten postcapillary mesenteric venules (30 microns diameter) per animal were observed using intravital microscopy. Macroscopic visible intestinal ulceration was scored and faecal pH of different sections of the small bowel was determined.

RESULTS

Small intestinal faecal pH was 8.5 in controls and 8.0 in indomethacin treated animals. Indomethacin significantly changed microcirculatory parameters: there was a 2.3-fold increase in leucocyte adherence, a 3.2-fold increase in leucocyte emigration, and a 20% reduction in shear rate. Application of various diets or diet combinations resulted in variations in faecal pH ranging from 7.8 to 8.8 which were inversely correlated with macroscopic ulcerations (r = -0.67). Leucocyte adherence was attenuated with increased pH and augmented with decreased pH (r = -0.55). Venular wall shear rate was positively correlated with faecal pH (r = 0.48) while leucocyte emigration showed no correlation. Leucocyte rolling velocity was not significantly altered. Normalisation of faecal pH by different alkalising drugs induced a significant decrease in leucocyte adherence in standard fed, indomethacin treated rats.

CONCLUSIONS

Faecal pH is lowered in the indomethacin model of long lasting ileitis in rats, which is similar to human inflammatory bowel disease. Alkalisation of faecal pH due to different diets or alkalising drugs reduces indomethacin induced leucocyte endothelial cell adhesion and macroscopic intestinal damage. These results may provide a rationale for the therapeutic effect of enteral diets in Crohn's disease.

摘要

背景

近期研究表明,与健康对照相比,炎症性肠病患者的粪便pH值呈酸化状态。在健康志愿者中,要素饮食可影响粪便pH值、粪便菌群及胆汁酸浓度。

目的

评估粪便pH值变化在吲哚美辛诱导的大鼠持续性回肠炎中对白细胞-内皮细胞黏附的作用。

方法

皮下注射吲哚美辛(7.5毫克/千克),间隔24小时注射两次。在炎症诱导前及诱导后10天直至实验结束,大鼠要么喂食相同饮食,要么在诱导时改变饮食。使用活体显微镜观察每只动物的10条肠系膜后微静脉(直径30微米)。对肉眼可见的肠道溃疡进行评分,并测定小肠不同节段的粪便pH值。

结果

对照组小肠粪便pH值为8.5,吲哚美辛处理组动物为8.0。吲哚美辛显著改变了微循环参数:白细胞黏附增加2.3倍,白细胞游出增加3.2倍,切变率降低20%。应用不同饮食或饮食组合导致粪便pH值在7.8至8.8之间变化,这与肉眼可见的溃疡呈负相关(r = -0.67)。白细胞黏附随pH值升高而减弱,随pH值降低而增强(r = -0.55)。微静脉壁切变率与粪便pH值呈正相关(r = 0.48),而白细胞游出无相关性。白细胞滚动速度无显著改变。不同碱化药物使粪便pH值正常化可导致标准饮食、吲哚美辛处理的大鼠白细胞黏附显著降低。

结论

在大鼠持续性回肠炎的吲哚美辛模型中,粪便pH值降低,这与人类炎症性肠病相似。不同饮食或碱化药物导致的粪便pH值碱化可减少吲哚美辛诱导的白细胞-内皮细胞黏附和肉眼可见的肠道损伤。这些结果可能为肠内饮食对克罗恩病的治疗作用提供理论依据。

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