（L）-精氨酸、（L）-NAME 和别嘌醇对大鼠肠缺血/再灌注损伤的影响。

Effects of oral administration of (L)-arginine, (L)-NAME and allopurinol on intestinal ischemia/reperfusion injury in rats.

机构信息

Laboratory of Experimental Surgery and Surgery Research "N. Christeas", Medical School, National and Kapodistrian University of Athens, Greece.

出版信息

Life Sci. 2011 Jun 6;88(23-24):1070-6. doi: 10.1016/j.lfs.2011.04.009. Epub 2011 Apr 30.

DOI:10.1016/j.lfs.2011.04.009

PMID:21565201

Abstract

AIMS

Intestinal ischemia/reperfusion (I/R) injury is implicated in many clinical conditions, and it performs a fundamental role in their pathophysiologies. Oral administration of antioxidants and nitric oxide (NO) donors ameliorate intestinal injury. Here, the effects of l-arginine, allopurinol and N(G)-nitro-l-arginine methyl ester (l-NAME) were investigated.

MAIN METHODS

One hundred twenty-eight male Wistar rats were separated into 4 groups and subjected to occlusion of the superior mesenteric artery for 60 min. The Control group did not receive any substance before the surgical operation. However, the 3 other groups received the following: l-arginine (800 mg/kg body weight; l-Arg group), l-NAME (50mg/kg; l-NAME group) or allopurinol (100mg/kg; Allo group). Each substance was given by mouth in 3 equal doses 24, 12 and 1h before the surgical operation. Each group was then divided into 4 subgroups, which underwent different durations of reperfusion (0, 1, 8 or 24h). At the end of each time point, blood and tissue samples were collected, and histological examinations were performed. Serum nitrite and catalase, intestinal tissue myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) levels were determined.

KEY FINDINGS

At each reperfusion time point, the Allo group exhibited the mildest histological lesions in contrast to the l-NAME group, which showed the most severe lesions. MPO was decreased significantly in the Allo and l-Arg groups during reperfusion, and allopurinol administration caused earlier and stronger effect. iNOS and NT levels were higher in the l-Arg group and lower in the Allo group. Serum nitrite and catalase were increased in the l-NAME group after 24h.

SIGNIFICANCE

Oral administration of allopurinol exerted a strong and protective effect on the intestinal tissue that was subjected to I/R earlier than l-arginine. This finding was also supported with the MPO, iNOS and NT data.

摘要

目的

肠缺血/再灌注（I/R）损伤与许多临床情况有关，并在其病理生理学中起重要作用。口服抗氧化剂和一氧化氮（NO）供体可改善肠损伤。本研究旨在探讨 l-精氨酸、别嘌呤醇和 N(G)-硝基-l-精氨酸甲酯（l-NAME）的作用。

方法

将 128 只雄性 Wistar 大鼠分为 4 组，夹闭肠系膜上动脉 60 分钟。对照组在手术前不接受任何物质。然而，另外 3 组分别接受以下处理：l-精氨酸（800mg/kg 体重；l-Arg 组）、l-NAME（50mg/kg；l-NAME 组）或别嘌呤醇（100mg/kg；Allo 组）。每种物质在手术前 24、12 和 1 小时口服 3 次等量。然后，每组再分为 4 个亚组，分别接受不同时间的再灌注（0、1、8 或 24 小时）。在每个时间点结束时，收集血液和组织样本，并进行组织学检查。测定血清亚硝酸盐和过氧化氢酶、肠组织髓过氧化物酶（MPO）、诱导型一氧化氮合酶（iNOS）和硝基酪氨酸（NT）水平。

主要发现

在每个再灌注时间点，与 l-NAME 组相比，Allo 组的组织学损伤最轻，而 l-NAME 组的损伤最严重。在再灌注期间，Allo 和 l-Arg 组的 MPO 显著降低，且别嘌呤醇的作用出现更早、更强。l-Arg 组的 iNOS 和 NT 水平较高，Allo 组的水平较低。l-NAME 组在 24 小时后血清亚硝酸盐和过氧化氢酶增加。