Filaretova L P, Bagaeva T R, Morozova O Y, Zelena D
Endocr Regul. 2014 Oct;48(4):163-72. doi: 10.4149/endo_2014_04_163.
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.
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.
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.
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.
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。
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。
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。
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。