慢性酒精中毒条件下一氧化氮代谢模型

A. Mykytenko
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引用次数: 0

摘要

实验表明,乙醇影响大鼠一氧化氮的产生。然而,一氧化氮可以通过削弱乙醇对肝脏微循环的有害作用来起到保护作用,也可以通过活性形式的氮来导致肝脏损伤。本研究旨在研究慢性酒精中毒大鼠模型条件下一氧化氮循环的变化。实验对象为30只体重180-220 g的成年雄性Wistar大鼠。实验动物分为2组:对照组(n=6);II组:酒精性肝炎动物(n=24),采用强制间歇酒精化5天的方法建模,2天后重复以4 ml/kg体重的速率在5%葡萄糖溶液中腹腔注射16.5%乙醇溶液。在硫喷妥钠麻醉下,分别于第10、14、21、28天右心室取血退出实验。测定了大鼠肝脏匀浆中no合酶诱导型和组成型同工型的活性,测定了碱土和碱土金属中亚硝酸盐、亚硝基硫醇和过氧亚硝酸盐的浓度,测定了亚硝酸盐还原酶、硝酸还原酶和精氨酸酶的活性。慢性酒精中毒模型持续10-28天,导致一氧化氮的形成和代谢受到破坏,主要形成其有毒代谢物,如过氧亚硝酸盐和亚硝酸盐,这威胁到肝脏中亚硝化应激的发展。实验第10 ~ 28天,慢性酒精中毒大鼠肝脏中精氨酸代谢的精氨酸酶依赖通路活性急剧下降,表明Krebs-Handzeleit循环中的脱氨过程被破坏。关键词:亚硝酸盐,no合酶,过氧亚硝酸盐,酒精,肝脏,大鼠。
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Metabolism of nitric oxide under the conditions chronic alcohol intoxication modelling
It was experimentally shown that ethanol affects the production of nitric oxide in rats. However, nitric oxide can have both a protective effect by weakening the harmful effect of ethanol on the microcirculation of the liver, and lead to liver damage by active forms of nitrogen. The purpose of the study is to study changes in the nitric oxide cycle under the conditions of modeling chronic alcohol intoxication in rats. Experiments were performed on 30 white, mature male Wistar rats, weighing 180–220 g. The animals were divided into 2 groups: I – control (n=6); II group – animals with alcoholic hepatitis (n=24) modelled by the method of forced intermittent alcoholization for 5 days, with a repeat after two days by intraperitoneal injection of a 16.5% ethanol solution in a 5% glucose solution, at the rate of 4 ml/kg of body weight. Animals were removed from the experiment on days 10, 14, 21 and 28 by taking blood from the right ventricle of the heart under thiopental anesthesia. The activity of inducible and constitutive isoforms of NO-synthase, concentration of nitrite, nitrosothiols and peroxynitrites of alkali and alkaline earth metals, the activity of nitrite reductase, nitrate reductase and arginase were determined in rat liver homogenate. Chronic alcohol intoxication modelling for 10–28 days leads to a violation of the formation and metabolism of nitric oxide with the predominant formation of its toxic metabolites, such as peroxynitrites and nitrites, which threatens the development of nitrosative stress in the liver. Chronic alcohol intoxication on the 10th–28th days of the experiment is accompanied by a sharp decrease in the activity of the arginase-dependent pathway of arginine metabolism in the liver of rats, which indicates a violation of the deamination processes in the Krebs-Handzeleit cycle. Keywords: nitrites, NO-synthase, peroxynitrite, alcohol, liver, rats.
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来源期刊
CiteScore
1.10
自引率
0.00%
发文量
32
期刊介绍: The Tokai Journal of Experimental and Clinical Medicine, also referred to as Tokai Journal, is an official quarterly publication of the Tokai Medical Association. Tokai Journal publishes original articles that deal with issues of clinical, experimental, socioeconomic, cultural and/or historical importance to medical science and related fields. Manuscripts may be submitted as full-length Original Articles or Brief Communications. Tokai Journal also publishes reviews and symposium proceedings. Articles accepted for publication in Tokai Journal cannot be reproduced elsewhere without written permission from the Tokai Medical Association. In addition, Tokai Journal will not be held responsible for the opinions of the authors expressed in the published articles.
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