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谷氨酰胺能否减少细菌移位?在两种肠道屏障受损动物模型中的研究。

Does glutamine reduce bacterial translocation? A study in two animal models with impaired gut barrier.

作者信息

Foitzik T, Kruschewski M, Kroesen A J, Hotz H G, Eibl G, Buhr H J

机构信息

Chirurgische Klinik I (Allgemein-, Gefäss- und Thoraxchirurgie), Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany,

出版信息

Int J Colorectal Dis. 1999 Aug;14(3):143-9. doi: 10.1007/s003840050200.

Abstract

Failure of intestinal barrier function and subsequent translocation of bacteria from the gut are believed to play a decisive role in the development of systemic septic complications, for example, following major trauma or major abdominal surgery. This study evaluated: (a) the effect of glutamine on colonic microcirculation and electrophysiological parameters reflecting gut barrier function, (b) the translocation of live bacteria to extraintestinal organs, and (c) disease outcome in two animal models with impaired gut barrier function. Severe acute pancreatitis or colitis was induced in rats randomized for therapy with or without glutamine (0.5 g/kg daily). After 48 h one animal group was prepared for intravital microscopy of colonic capillary blood flow and electrophysiological measurement of gut permeability; another was killed after 96 h for histological and microbiological examination. In animals with pancreatitis, glutamine (Gln) supplementation significantly improved gut permeability, i.e., Gln increased colonic transmucosal resistance from 67+/-7 to 92+/-3 Omega/cm(2) and decreased mannitol flux through the epithelium by 53%. Capillary blood flow in the colonic mucosa was improved by 25%. The prevalence of pancreatic infections was reduced from 86% in animals on standard parenteral nutrition to 33% in animals given the Gln-enriched diet (P<0.05); mortality decreased by 32%. In colitis, Gln had no significant effect on these parameters except for improving colonic capillary blood flow in colon segments not adjacent to the major injury site. Glutamine supplementation improves colonic capillary blood flow, stabilizes gut permeability, and reduces secondary pancreatic infections and mortality in severe rodent pancreatitis, but it is not helpful in colitis. This confirms previous reports that glutamine stabilizes gut barrier function only in certain diseases. Our experimental data strongly suggest that acute pancreatitis (rather than colitis) is one of the diseases with gut barrier dysfunction in which glutamine substitution may be helpful to reduce bacterial translocation and should therefore be tested in a controlled clinical trial.

摘要

肠屏障功能衰竭以及随后细菌从肠道易位被认为在全身感染性并发症的发生发展中起决定性作用,例如在严重创伤或腹部大手术后。本研究评估了:(a)谷氨酰胺对结肠微循环以及反映肠道屏障功能的电生理参数的影响;(b)活菌向肠外器官的易位;(c)在两种肠道屏障功能受损的动物模型中的疾病转归。将大鼠随机分为接受或不接受谷氨酰胺(每日0.5 g/kg)治疗组,诱导其发生重症急性胰腺炎或结肠炎。48小时后,一组动物准备用于结肠毛细血管血流的活体显微镜检查以及肠道通透性的电生理测量;另一组在96小时后处死,进行组织学和微生物学检查。在患有胰腺炎的动物中,补充谷氨酰胺(Gln)显著改善了肠道通透性,即Gln使结肠跨黏膜电阻从67±7增加至92±3Ω/cm²,并使甘露醇通过上皮的通量降低了53%。结肠黏膜的毛细血管血流改善了25%。胰腺感染的发生率从接受标准肠外营养的动物中的86%降至给予富含Gln饮食的动物中的33%(P<0.05);死亡率降低了32%。在结肠炎中,Gln对这些参数没有显著影响,除了改善未邻近主要损伤部位的结肠段的结肠毛细血管血流。补充谷氨酰胺可改善结肠毛细血管血流,稳定肠道通透性,并降低重症啮齿动物胰腺炎的继发性胰腺感染和死亡率,但对结肠炎无效。这证实了先前的报道,即谷氨酰胺仅在某些疾病中稳定肠道屏障功能。我们的实验数据强烈表明,急性胰腺炎(而非结肠炎)是肠道屏障功能障碍的疾病之一,在这种疾病中谷氨酰胺替代可能有助于减少细菌易位,因此应在对照临床试验中进行测试。

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