关键词: Anesthesia Inflammatory response Murine trauma model Organ dysfunction

来  源:   DOI:10.1007/s00068-024-02583-y

Abstract:
OBJECTIVE: Multiple murine studies modelling the immuno-pathophysiological consequences of trauma, shock, burn or sepsis were performed during the last decades. Almost every animal model requires anesthesia for practical and ethical reasons. Furthermore, often, corresponding control groups involve untreated animals without or with a limited exposure to anesthetics. However, the influences of anesthetic drugs on immuno-pathophysiological reactions remain insufficiently investigated. Therefore, we aimed to closer characterize the anesthetic impact exemplified by sevoflurane on the organ performance in mice and thereby investigate the influence of anesthesia itself on major outcome parameters in animal studies.
METHODS: C57/BL6 mice were subjected either to 270 min of sevoflurane narcosis or directly euthanized. Plasma, BAL-fluids, lungs, kidneys, liver and intestine were collected and examined for immunological, functional and morphological changes.
RESULTS: Systemic levels of the cytokine keratinocyte chemoattractant (KC) were raised in the narcosis group, while concentrations of high mobility group box protein 1 (HMGB-1) as a major inflammatory marker were reduced. In the lungs, levels of HMGB-1 and interleukin 6 (IL-6) were reduced. In contrast, systemic concentrations of intestinal fatty acid binding-protein (i-FABP) as an intestinal damage marker were elevated. Furthermore, liver-type fatty acid binding-protein (L-FABP) levels were lower in the narcosis animals, and inflammatory markers were reduced in liver tissues. Anesthesia also ameliorated the inflammatory reaction in renal tissues, while plasma levels of urea and creatinine were elevated, reflecting either dehydration and/or impaired renal function.
CONCLUSIONS: As anesthesia with sevoflurane exhibited distinct effects in different organs, it is difficult to predict its specific impact on targets of interest in in vivo studies. Therefore, further studies are required to clarify the effects of different anesthetic drugs. Overall, the inclusion of a control group subjected to the same anesthesia protocol as the experimental groups of interest seems helpful to precisely define the inherent impact of the anesthetic when investigating immuno-pathophysiologic conditions in vivo.
摘要:
目的:多种小鼠研究模拟创伤的免疫病理生理后果,震惊,烧伤或败血症发生在过去几十年.几乎每个动物模型都需要出于实际和道德原因进行麻醉。此外,经常,相应的对照组包括未接受或有限暴露于麻醉剂的未经治疗的动物.然而,麻醉药物对免疫病理生理反应的影响仍未得到充分研究。因此,我们旨在更详细地描述七氟醚对小鼠器官表现的麻醉影响,从而研究麻醉本身对动物研究中主要结局参数的影响.
方法:C57/BL6小鼠经受270分钟的七氟醚麻醉或直接安乐死。血浆,BAL液,肺,肾脏,收集肝脏和肠道并进行免疫学检查,功能和形态变化。
结果:麻醉组细胞因子角质形成细胞趋化因子(KC)的全身水平升高,而作为主要炎症标志物的高迁移率族框蛋白1(HMGB-1)的浓度降低。在肺部,HMGB-1和白细胞介素6(IL-6)水平降低。相比之下,作为肠道损伤标志物的肠道脂肪酸结合蛋白(i-FABP)的全身浓度升高.此外,肝型脂肪酸结合蛋白(L-FABP)水平较低的麻醉动物,肝脏组织中炎症标志物减少。麻醉还改善了肾组织的炎症反应,而血浆尿素和肌酐水平升高,反映脱水和/或肾功能受损。
结论:七氟醚麻醉对不同器官有明显影响,在体内研究中,很难预测其对目标目标的具体影响。因此,需要进一步的研究来阐明不同麻醉药物的作用。总的来说,在研究体内免疫病理生理条件时,纳入与感兴趣的实验组相同麻醉方案的对照组似乎有助于准确定义麻醉药的固有影响.
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