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系统性炎症对大脑的影响并未被小鼠的布洛芬治疗完全缓解。

The brain consequences of systemic inflammation were not fully alleviated by ibuprofen treatment in mice.

机构信息

Student Research Committee, Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Pharmacol Rep. 2021 Feb;73(1):130-142. doi: 10.1007/s43440-020-00141-y. Epub 2020 Jul 21.

Abstract

BACKGROUND

Extensive data point to the immune system as an important factor underlying the pathogenesis of brain diseases. Epidemiological studies have shown that long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) significantly reduces the onset and progression of Alzheimer's disease. The present study aimed to investigate whether ibuprofen (IBU) is able to prevent the long-lasting alterations of brain function induced by systemic inflammation.

METHODS

Mice received intraperitoneal injections of lipopolysaccharide (LPS; 250 µg/kg/day) for seven consecutive days. Ibuprofen administration (40 mg/kg/day) was started three days before the LPS injections and continued until the last day of LPS injection. Within the next 2 weeks, mice performances on the behavioral tests were evaluated, and then brain tissue samples for biochemical analyses were collected.

RESULTS

The findings showed that ibuprofen significantly improved mice's performance in the passive avoidance test and reduced anxiety- and depressive-like behaviors. However, ibuprofen could not significantly improve spatial memory in the Morris water maze test and recognition ability in the novel object recognition test. TNF-α and IL-1β cytokines levels and malondialdehyde (MDA) concentration in the hippocampal tissues of LPS-treated mice were significantly lowered by ibuprofen treatment, whereas no significant effects on IL-10 production and hippocampal BDNF levels were observed. In addition, ibuprofen did not significantly reduce amyloid-β levels in the hippocampus of LPS-treated animals.

CONCLUSION

Overall, the findings of the present study suggest that some, but not all, of the adverse effects of systemic inflammation are alleviated by ibuprofen treatment.

摘要

背景

大量数据表明免疫系统是脑疾病发病机制的重要因素。流行病学研究表明,长期使用非甾体抗炎药(NSAIDs)可显著降低阿尔茨海默病的发病和进展。本研究旨在探讨布洛芬(IBU)是否能够预防全身炎症引起的大脑功能持久改变。

方法

小鼠连续 7 天腹腔注射脂多糖(LPS;250µg/kg/天)。IBU 给药(40mg/kg/天)于 LPS 注射前 3 天开始,并持续至 LPS 注射的最后一天。在接下来的 2 周内,评估小鼠在行为测试中的表现,然后收集脑组织样本进行生化分析。

结果

研究结果表明,布洛芬可显著改善小鼠在被动回避测试中的表现,减轻焦虑和抑郁样行为。然而,布洛芬不能显著改善 Morris 水迷宫测试中的空间记忆和新物体识别测试中的识别能力。LPS 处理小鼠海马组织中的 TNF-α和 IL-1β细胞因子水平和丙二醛(MDA)浓度经布洛芬治疗后显著降低,而对 IL-10 产生和海马 BDNF 水平无明显影响。此外,布洛芬不能显著降低 LPS 处理动物海马中的淀粉样蛋白-β水平。

结论

总的来说,本研究结果表明,布洛芬治疗减轻了全身炎症的一些但不是所有的不良影响。

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