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[谷氨酰胺和ω-3多不饱和脂肪酸对大鼠肠缺血再灌注损伤时肠通透性及肺细胞凋亡的影响]

[Impact of glutamine and ω-3 polyunsaturated fatty acids on intestinal permeability and lung cell apoptosis during intestinal ischemia-reperfusion injury in a rat model].

作者信息

He Gui-zhen, Dong Liang-guang, Cui Xiao-yu, Chen Xue-feng, Zhang Rui

机构信息

Department of Enteral and Parenteral Nutrition, Peking Union Medical College Hospital, CAMS and PUMC, Beijing, China.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2012 May;15(5):484-9.

Abstract

OBJECTIVE

To investigate the impact of intestinal lymphatic vessels ligation and different enteral nutrition support during ischemia/reperfusion on intestinal permeability, systemic inflammatory response and pulmonary dysfunction in a rat model.

METHODS

Seventy-two Sprague-Dawley male rats were randomized into normal diet group, regular enteral nutrition group, glutamine-enriched group, 0-3 polyunsaturated fatty acids (wo-3PUFA) group, and sham control after gastrostomy. All the enteral nutrition group were isocaloric (1046 kJ kg-' d-1) and isonitrogenous (1.8 g N kg-' d-'). After enteral nutrition for 7 days, the rats were subjected to intestinal ischemia for 60 min, or ischemia plus mesenteric lymph duct ligation except for the sham group followed by 3 days of nutrition (72 h). Intestinal permeability (lactose/mannitol ratio in the urine, L/M) was determined on the 5th, 7th and 9th day after gastrostomy. The levels of serum diamine oxidase, endotoxin, cytokines, ALT and AST were detected at the 11th day after gastrostomy. Mucosal thickness was measured using small intestine and villusheight. Myeloperoxidase (MPO), nitric oxide (NO), NO synthase, and apoptotic index were detected in lung tissue.

RESULTS

Ischemia for 60 min could cause intestinal injury. Intestinal permeability(L/M)was increased significantly in every group on the first day after ischemia (P<0.05). However, L/M decreased significantly 3 days after ischemia (P<0.05). The groups with Glu and o-3PUFA-enriched nutrition almost restored to normal level (P>0.05). The level of L/M in lymphatic ligation group was significantly lower than non-ligation group (P<0.05). The levels of endotoxin and cytokine were reduced, mucosal thickness and villous height were significantly higher (P<0.05) in the groups of Glu and o-3PUFA-enriched nutrition compared with enteral nutrition and normal diet groups during intestinal ischemia-reperfusion injury. MPO, NO, NOS and the apoptosis index of lung tissue decreased in the groups of Glu and o-3PUFA-enriched as well as after lymph duct ligation (P<0.05).

CONCLUSIONS

The distant tissue-lung damage and systemic inflammation caused by intestinal ischemia-reperfusion injury may be related to some factors in the intestinal lymph. Blocking the gut-lymph pathway and/or adding Glu and o-3PUFA in enteral nutrition may reduce intestinal permeability and endotoxin, increase mucosal thickness, attenuate the systemic inflammatory reaction, and prevent lung injury

摘要

目的

在大鼠模型中研究肠淋巴管结扎及缺血/再灌注期间不同肠内营养支持对肠通透性、全身炎症反应和肺功能障碍的影响。

方法

将72只雄性Sprague-Dawley大鼠随机分为正常饮食组、常规肠内营养组、富含谷氨酰胺组、0-3多不饱和脂肪酸(ω-3PUFA)组和假手术对照组(造瘘后)。所有肠内营养组均为等热量(1046 kJ·kg⁻¹·d⁻¹)和等氮量(1.8 g N·kg⁻¹·d⁻¹)。肠内营养7天后,除假手术组外,大鼠接受60分钟的肠缺血,或缺血加肠系膜淋巴管结扎,随后进行3天的营养支持(72小时)。在造瘘后第5、7和9天测定肠通透性(尿中乳糖/甘露醇比值,L/M)。在造瘘后第11天检测血清二胺氧化酶、内毒素、细胞因子、谷丙转氨酶和谷草转氨酶水平。用小肠测量黏膜厚度和绒毛高度。检测肺组织中的髓过氧化物酶(MPO)、一氧化氮(NO)、一氧化氮合酶和凋亡指数。

结果

60分钟的缺血可导致肠损伤。缺血后第一天,每组的肠通透性(L/M)均显著升高(P<0.05)。然而,缺血3天后L/M显著降低(P<0.05)。富含谷氨酰胺和ω-3PUFA营养组几乎恢复到正常水平(P>0.05)。淋巴管结扎组的L/M水平显著低于未结扎组(P<0.05)。在肠缺血-再灌注损伤期间,与肠内营养组和正常饮食组相比,富含谷氨酰胺和ω-3PUFA营养组的内毒素和细胞因子水平降低,黏膜厚度和绒毛高度显著更高(P<0.05)。富含谷氨酰胺和ω-3PUFA营养组以及淋巴管结扎后肺组织的MPO、NO、NOS和凋亡指数降低(P<0.05)。

结论

肠缺血-再灌注损伤引起的远处组织-肺损伤和全身炎症可能与肠淋巴中的某些因素有关。阻断肠-淋巴途径和/或在肠内营养中添加谷氨酰胺和ω-3PUFA可能降低肠通透性和内毒素,增加黏膜厚度,减轻全身炎症反应,并预防肺损伤。

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