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益生菌通过激活 AKT 信号通路来减少便秘引起的抑郁行为。

Probiotics decrease depressive behaviors induced by constipation via activating the AKT signaling pathway.

机构信息

Laboratory of Morphology, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China.

Medical Technology School, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China.

出版信息

Metab Brain Dis. 2018 Oct;33(5):1625-1633. doi: 10.1007/s11011-018-0269-4. Epub 2018 Jun 15.

Abstract

Chronic constipation is often accompanied by emotional disorders such as depression and anxiety. The aim of this study was to determine whether administration of a multispecies probiotic can decrease depressive behaviors through the gut-brain axis and identify any underlying mechanisms. A mouse model of constipation induced by loperamide (5 mg·kg,i.p.) was used. For that purpose, 36 ICR male mice were divided into three groups: control, constipation and probiotic groups. The probiotic group received treatment with a probiotic once per day for 14 days via a gavage. All other groups were given an equal volume of normal saline. The fecal parameters and intestinal transit ratio were recorded. The forced swimming test and tail suspension test were used to detect changes in depressive behaviors. Total superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) levels were measured by assay kits. We also detected neuronal survival, as well as phosphorylated Ser/Thr protein kinase (p-AKT), Bcl-2, Bcl-2 associated X protein (Bax) and cleaved caspase-3 levels in the hippocampus. The results showed that administration of a probiotic could ameliorate depressive behaviors and relieve neuronal cell injury in the hippocampal CA3 regions. Moreover, probiotic treatment decreased MDA levels and increased SOD activity. Furthermore, probiotic administration increased p-AKT and Bcl-2 levels in the hippocampus of the constipated mice, while decreasing the concentrations of Bax and cleaved caspase-3, so as to inhibit the neural apoptosis. In the present study, we confirm that probiotics can alleviate depression induced by constipation through protecting neuronal health via activation of the AKT signaling pathway.

摘要

慢性便秘常伴有情绪障碍,如抑郁和焦虑。本研究旨在确定多菌种益生菌是否可以通过肠脑轴来减轻抑郁行为,并确定潜在的机制。使用洛哌丁胺(5mg·kg,ip)诱导的便秘小鼠模型。为此,将 36 只 ICR 雄性小鼠分为三组:对照组、便秘组和益生菌组。益生菌组每天通过灌胃接受一次益生菌治疗,共 14 天。其他所有组均给予等量的生理盐水。记录粪便参数和肠道转运比。使用强迫游泳试验和悬尾试验检测抑郁行为的变化。通过试剂盒测量总超氧化物歧化酶(T-SOD)活性和丙二醛(MDA)水平。我们还检测了海马体中的神经元存活以及磷酸化丝氨酸/苏氨酸蛋白激酶(p-AKT)、B 细胞淋巴瘤 2(Bcl-2)、Bcl-2 相关 X 蛋白(Bax)和半胱天冬酶-3 的裂解水平。结果表明,益生菌的给予可以改善抑郁行为,并缓解海马 CA3 区的神经元细胞损伤。此外,益生菌治疗降低了 MDA 水平并增加了 SOD 活性。此外,益生菌给药增加了便秘小鼠海马体中的 p-AKT 和 Bcl-2 水平,同时降低了 Bax 和半胱天冬酶-3 的浓度,从而抑制了神经细胞凋亡。在本研究中,我们证实益生菌可以通过激活 AKT 信号通路来保护神经元健康,从而缓解便秘引起的抑郁。

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