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富含鱼油的脂肪乳剂调节脓毒症后的神经炎症反应,预防长期认知功能障碍。

Fish oil-rich lipid emulsion modulates neuroinflammation and prevents long-term cognitive dysfunction after sepsis.

机构信息

Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, University of South Santa Catarina, Tubarão, SC, Brazil.

Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA.

出版信息

Nutrition. 2020 Feb;70:110417. doi: 10.1016/j.nut.2018.12.003. Epub 2018 Dec 7.

Abstract

OBJECTIVES

Sepsis is a severe organic dysfunction caused by an infection that affects the normal regulation of several organ systems, including the central nervous system. Inflammation and oxidative stress play crucial roles in the development of brain dysfunction in sepsis. The aim of this study was to determine the effect of a fish oil (FO)-55-enriched lipid emulsion as an important anti-inflammatory compound on brain dysfunction in septic rats.

METHODS

Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with FO (600 µL/kg after CLP) or vehicle (saline; sal). Animals were divided into sham+sal, sham+FO, CLP+sal and CLP+FO groups. At 24 h and 10 d after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of interleukin (IL)-1β and IL-10, blood-brain barrier permeability, nitrite/nitrate concentration, myeloperoxidase activity, thiobarbituric acid reactive species formation, protein carbonyls, superoxide dismutase and catalase activity, and brain-derived neurotrophic factor levels. Behavioral tasks were performed 10 d after surgery.

RESULTS

FO reduced BBB permeability in the prefrontal cortex and total cortex of septic rats, decreased IL-1β levels and protein carbonylation in all brain structures, and diminished myeloperoxidase activity in the hippocampus and prefrontal cortex. FO enhanced brain-derived neurotrophic factor levels in the hippocampus and prefrontal cortex and prevented cognitive impairment.

CONCLUSIONS

FO diminishes the negative effect of polymicrobial sepsis in the rat brain by reducing inflammatory and oxidative stress markers.

摘要

目的

败血症是一种由感染引起的严重器官功能障碍,会影响包括中枢神经系统在内的多个器官系统的正常调节。炎症和氧化应激在败血症引起的脑功能障碍发展中起着至关重要的作用。本研究旨在确定富含鱼油(FO)-55 的脂肪乳剂作为一种重要的抗炎化合物对败血症大鼠脑功能障碍的影响。

方法

Wistar 大鼠通过盲肠结扎和穿孔(CLP)或假手术(对照)引发败血症,并经口给予 FO(CLP 后 600 μL/kg)或载体(盐水;sal)。动物分为假手术+sal、假手术+FO、CLP+sal 和 CLP+FO 组。手术后 24 h 和 10 d 时,取出海马体、前额皮质和全皮质,测定白细胞介素(IL)-1β和 IL-10 水平、血脑屏障通透性、亚硝酸盐/硝酸盐浓度、髓过氧化物酶活性、硫代巴比妥酸反应性物质形成、蛋白羰基、超氧化物歧化酶和过氧化氢酶活性以及脑源性神经营养因子水平。手术后 10 d 进行行为任务。

结果

FO 降低了败血症大鼠前额皮质和全皮质的血脑屏障通透性,降低了所有脑结构中的 IL-1β 水平和蛋白羰基化,减少了海马体和前额皮质中的髓过氧化物酶活性。FO 增加了海马体和前额皮质中的脑源性神经营养因子水平,并预防了认知障碍。

结论

FO 通过降低炎症和氧化应激标志物,减轻了多微生物败血症对大鼠大脑的负面影响。

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