中国中药杂志

2021, v.46(19) 5088-5095

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茯苓酸性多糖抗抑郁作用及其调节神经递质和NLRP3通路机制研究
Antidepressant effect of acidic polysaccharides from Poria and their regulation of neurotransmitters and NLRP3 pathway

陈可琢;陈实;任洁贻;林诗;肖明军;成立;叶晓川;
CHEN Ke-zhuo;CHEN Shi;REN Jie-yi;LIN Shi;XIAO Ming-jun;CHENG Li;YE Xiao-chuan;School of Pharmacy, Hubei University of Chinese Medicine;Hubei Key Laboratory of Chinese Medicine Resources and Chinese Medicine Chemistry;

摘要(Abstract):

慢性不可预知温和应激(chronic unpredictable mild stress, CUMS)结合孤养模式构建抑郁模型大鼠,以行为学指标评价大鼠抑郁行为,苏木精-伊红染色法(hematoxylin-eosin staining, HE)观察海马CA3区和前额叶皮质的神经元细胞数目和形态,酶联免疫吸附(ELISA)法测定脑源性神经营养因子(brain-derivedneurotrophic factor, BDNF)、5-羟色胺(5-hydroxytryptamine, 5-HT)、5-羟吲哚乙酸(5-hydroxyindoleacetic acid, 5-HIAA)、多巴胺(dopamine, DA)、去甲肾上腺素(norepinephrine, NE)、谷氨酸(glutamic acid, GLU)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-18(interleukin-18,IL-18)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;实时定量-聚合酶链反应(RT-PCR)法和蛋白质免疫印迹(Western blot)法分别检测与NLRP3通路中相关mRNA水平和蛋白表达。结果显示,与模型组比较,茯苓酸性多糖低、中、高剂量组(0.1、0.3、0.5 g·kg~(-1)·d~(-1))均能改善大鼠的抑郁样行为,促进神经元细胞数目增多,提高海马组织中BDNF、5-HT、5-HIAA、DA、NE的水平,降低GLU水平与血清IL-1β、IL-18、TNF-α促炎因子水平;各给药组能不同程度降低ASC、caspase-1、IL-1β、IL-18 mRNA表达水平和NLRP3、ASC、caspase-1、IL-1β、IL-18蛋白表达水平,同时升高pro-caspase-1、pro-IL-1β、pro-IL-18蛋白表达水平。以上结果表明,茯苓酸性多糖具有显著抗抑郁作用,其作用机制可能与调节神经递质和NLRP3炎症小体信号通路有关。
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.

关键词(KeyWords): 茯苓酸性多糖;抑郁症;慢性不可预知应激;神经递质;NLRP3通路
acidic polysaccharides from Poria;depressive disorder;chronic unpredictable mild stress(CUMS);neurotransmitters;NLRP3 pathway

Abstract:

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基金项目(Foundation): 国家重点研发计划项目(2017YFC1703004);; 湖北省技术创新专项重大项目(2019ACA121)

作者(Author): 陈可琢;陈实;任洁贻;林诗;肖明军;成立;叶晓川;
CHEN Ke-zhuo;CHEN Shi;REN Jie-yi;LIN Shi;XIAO Ming-jun;CHENG Li;YE Xiao-chuan;School of Pharmacy, Hubei University of Chinese Medicine;Hubei Key Laboratory of Chinese Medicine Resources and Chinese Medicine Chemistry;

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