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对胃糜烂的更广泛观察:对给予致胃溃疡剂量吲哚美辛的大鼠复杂躯体和行为变化的详细评估。

A wider view on gastric erosion: detailed evaluation of complex somatic and behavioral changes in rats treated with indomethacin at gastric ulcerogenic dose.

作者信息

Filaretova L P, Bagaeva T R, Morozova O Y, Zelena D

出版信息

Endocr Regul. 2014 Oct;48(4):163-72. doi: 10.4149/endo_2014_04_163.

DOI:10.4149/endo_2014_04_163
PMID:25512189
Abstract

OBJECTIVE

Gastric erosion is widespread side effect of nonsteroidal anti-inflammatory drugs. To examine the complexity of the brain-gut axis regulation, indomethacin-induced gastric erosion formation was studied in connection with somatic and behavioral changes.

METHODS

During a constant telemetric recording of heart rate, body temperature, and locomotion of male rats we examined the effects of 24 h fasting, indomethacin (35 mg/kg s.c.) injection, and refeeding at 4 h. Behavior was analyzed on elevated plus maze (EPM) at 24 h and somatic changes at 72 h.

RESULTS

Gastric erosion developed 4 h after indomethacin injection, healed 72 h later contrasted by large injury in the small intestine. As classical signs of chronic stress, body and thymus weight were reduced while adrenal weight was enhanced 72 h after indomethacin injection. Fasting by itself changed all telemetrically recorded parameters with most prominent decrease in heart rate. Indomethacin induced similar diminishing effects with earliest and strongest temperature decrease. As a sign of more anxious phenotype locomotion reducing effect of indomethacin injection was detected on EPM. The EPM-induced temperature elevation was missing in indomethacin-treated animals.

CONCLUSIONS

Fasting by itself induce somatic changes, which can make the animals more vulnerable to ulcerogenic stimuli. Development of indomethacin-induced gastrointestinal lesions happened in parallel with disturbances of heart rate, core body temperature, and chronic stress-like somatic changes as well as anxiety-like behavior. We have to be more aware of the existence of the brain-gut axis and should study changes in the whole body rather than focusing on a specific organ. elevated plus maze.

摘要

目的

胃糜烂是非甾体抗炎药广泛存在的副作用。为研究脑-肠轴调节的复杂性,我们结合躯体和行为变化对吲哚美辛诱导的胃糜烂形成进行了研究。

方法

在持续遥测雄性大鼠心率、体温和活动的过程中,我们检测了24小时禁食、注射吲哚美辛(35毫克/千克,皮下注射)以及4小时后重新喂食的影响。在24小时时通过高架十字迷宫(EPM)分析行为,在72小时时分析躯体变化。

结果

吲哚美辛注射后4小时出现胃糜烂,72小时后愈合,与之形成对比的是小肠出现严重损伤。作为慢性应激的典型体征,吲哚美辛注射72小时后体重和胸腺重量降低,而肾上腺重量增加。禁食本身改变了所有遥测记录的参数,心率下降最为显著。吲哚美辛产生了类似的递减效应,最早且最强烈的是体温下降。在EPM上检测到吲哚美辛注射有降低活动的作用,这是更焦虑表型的一个标志。在吲哚美辛处理的动物中,EPM诱导的体温升高消失。

结论

禁食本身会引起躯体变化,这会使动物更容易受到致溃疡刺激的影响。吲哚美辛诱导的胃肠道损伤的发生与心率、核心体温的紊乱以及慢性应激样躯体变化和焦虑样行为同时出现。我们必须更加意识到脑-肠轴的存在,应该研究全身的变化而不是只关注某个特定器官。高架十字迷宫。

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