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间充质干细胞条件培养基处理可改善小鼠术后认知功能障碍,其与脑组织中炎症、氧化应激的减少和 BDNF 表达的增加有关。

Amelioration of postoperative cognitive dysfunction in mice by mesenchymal stem cell-conditioned medium treatments is associated with reduced inflammation, oxidative stress and increased BDNF expression in brain tissues.

机构信息

Department of Anesthesiology, Affiliated Hospital of Guizhou Medical University, Guizhou, China.

Department of Anesthesiology, Affiliated Hospital of Guizhou Medical University, Guizhou, China.

出版信息

Neurosci Lett. 2019 Sep 14;709:134372. doi: 10.1016/j.neulet.2019.134372. Epub 2019 Jul 8.

Abstract

OBJECTIVE

Mesenchymal stem cells (MSCs) are widely used in regeneration and repair of various tissues and organs, and whether MSC-conditioned medium (MSC-CM) has protective effects in postoperative cognitive dysfunction (POCD) remains largely unknown. We aimed to assess the therapeutic effect and explore the mechanisms of MSC-CM therapy in a POCD mouse model.

METHODS

Sixty C57BL/6 mice were randomly assigned to 3 groups: control, POCD and POCD + MSC-CM. The POCD mouse model was established by left liver lobectomy. While mice in the control group were sham-operated, mice in the POCD + MSC-CM group were immediately administrated with MSC-CM after operation. The Morris water maze was used to determine cognitive function of mice at 1, 3, and 7 days after operation. The levels of IL-1β, IL-6, TNF-α and malondialdehyde in brain tissues at 3 days after operation were assessed by ELISA, while the protein level of brain derived neurotrophic factor (BDNF) was determined by western blot.

RESULTS

Left liver lobectomy induced POCD in mice resulted in decrease of cognitive function, increase of brain IL-1β, IL-6, TNF-α and malondialdehyde levels, and decreased BDNF expression, while administration of MSC-CM significantly reversed these changes.

CONCLUSION

MSC-CM ameliorates POCD in mice, and its protective roles are associated with reduced levels of inflammatory factors, attenuated oxidative stress, and increased BDNF expression.

摘要

目的

间充质干细胞(MSCs)广泛用于各种组织和器官的再生和修复,而 MSC 条件培养基(MSC-CM)在术后认知功能障碍(POCD)中是否具有保护作用尚不清楚。我们旨在评估 MSC-CM 治疗在 POCD 小鼠模型中的治疗效果并探索其机制。

方法

60 只 C57BL/6 小鼠被随机分为 3 组:对照组、POCD 组和 POCD+MSC-CM 组。通过左肝叶切除术建立 POCD 小鼠模型。对照组小鼠进行假手术,POCD+MSC-CM 组小鼠在手术后立即给予 MSC-CM。术后 1、3 和 7 天,使用 Morris 水迷宫确定小鼠的认知功能。通过 ELISA 评估术后 3 天脑组织中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和丙二醛(MDA)的水平,通过 Western blot 测定脑源性神经营养因子(BDNF)的蛋白水平。

结果

左肝叶切除术导致的 POCD 会降低小鼠的认知功能,增加大脑中的 IL-1β、IL-6、TNF-α 和 MDA 水平,并降低 BDNF 表达,而 MSC-CM 的给予则显著逆转了这些变化。

结论

MSC-CM 可改善 POCD 小鼠的认知功能,其保护作用与降低炎症因子水平、减轻氧化应激和增加 BDNF 表达有关。

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