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茯苓酸性多糖的抗抑郁作用及其对神经递质和NLRP3通路的调节

[Antidepressant effect of acidic polysaccharides from Poria and their regulation of neurotransmitters and NLRP3 pathway].

作者信息

Chen Ke-Zhuo, Chen Shi, Ren Jie-Yi, Lin Shi, Xiao Ming-Jun, Cheng Li, Ye Xiao-Chuan

机构信息

School of Pharmacy, Hubei University of Chinese Medicine Wuhan 430065, China.

School of Pharmacy, Hubei University of Chinese Medicine Wuhan 430065, China Hubei Key Laboratory of Chinese Medicine Resources and Chinese Medicine Chemistry Wuhan 430065, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2021 Oct;46(19):5088-5095. doi: 10.19540/j.cnki.cjcmm.20210610.705.

DOI:10.19540/j.cnki.cjcmm.20210610.705
PMID:34738405
Abstract

The rats were exposed to chronic unpredictable mild stress(CUMS) and kept in separate cages for inducing depressive disorder, which was judged by behavioral indicators. The number and morphology of neurons in hippocampal CA3 area and prefrontal cortex were observed by hematoxylin-eosin(HE) staining. The levels of brain-derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), norepinephrine(NE), glutamic acid(GLU), interleukin-1β(IL-1β), interleukin-18(IL-18), and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay(ELISA). Real-time polymerase chain reaction(RT-PCR) and Western blot were conducted to determine the mRNA and protein expression levels of related molecules in NLRP3 pathway. The results showed that compared with the model group, acidic polysaccharides from Poria at the low-, medium-, and high-doses(0.1, 0.3 and 0.5 g·kg(-1)·d(-1)) all improved the depression-like behavior of rats, increased the number of neurons and the levels of BDNF, 5-HT, 5-HIAA, DA, and NE in the hippocampus, and reduced GLU and serum IL-1β, IL-18, and TNF-α levels. The mRNA expression levels of ASC, caspase-1, IL-1β, and IL-18 and the protein expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in each medication group were down-regulated, whereas the protein expression levels of pro-caspase-1, pro-IL-1β, and pro-IL-18 were up-regulated. All these have indicated that acidic polysaccharides from Poria exerted the antidepressant effect possibly by regulating neurotransmitters and NLRP3 inflammasome signaling pathway.

摘要

将大鼠暴露于慢性不可预测轻度应激(CUMS)中,并将其单独饲养在笼子里以诱发抑郁障碍,通过行为指标进行判断。采用苏木精-伊红(HE)染色观察海马CA3区和前额叶皮质神经元的数量和形态。采用酶联免疫吸附测定(ELISA)检测脑源性神经营养因子(BDNF)、5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)、去甲肾上腺素(NE)、谷氨酸(GLU)、白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)和肿瘤坏死因子-α(TNF-α)的水平。进行实时聚合酶链反应(RT-PCR)和蛋白质免疫印迹法以测定NLRP3通路中相关分子的mRNA和蛋白质表达水平。结果显示,与模型组相比,低、中、高剂量(0.1、0.3和0.5 g·kg⁻¹·d⁻¹)的茯苓酸性多糖均改善了大鼠的抑郁样行为,增加了海马区神经元数量以及BDNF、5-HT、5-HIAA、DA和NE的水平,并降低了GLU以及血清IL-1β、IL-18和TNF-α水平。各给药组中ASC、半胱天冬酶-1、IL-1β和IL-18的mRNA表达水平以及NLRP3、ASC、半胱天冬酶-1、IL-1β和IL-18的蛋白质表达水平均下调,而前半胱天冬酶-1、前IL-1β和前IL-18的蛋白质表达水平上调。所有这些表明,茯苓酸性多糖可能通过调节神经递质和NLRP3炎性小体信号通路发挥抗抑郁作用。

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Front Pharmacol. 2022 Feb 14;13:793525. doi: 10.3389/fphar.2022.793525. eCollection 2022.