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开心散通过调节肠道菌群和减少神经元损伤改善D-半乳糖和Aβ诱导的阿尔茨海默病大鼠的认知障碍。

Kai-xin-san improves cognitive impairment in D-gal and Aβ induced ad rats by regulating gut microbiota and reducing neuronal damage.

作者信息

Wang Huijuan, Zhou Lifen, Zheng Qin, Song Yonggui, Huang Weihua, Yang Lin, Xiong Yongchang, Cai Zhinan, Chen Ying, Yuan Jinbin

机构信息

Key Lab of Modern Preparations of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.

Laboratory Animal Science and Technology Development Center, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.

出版信息

J Ethnopharmacol. 2024 Jul 15;329:118161. doi: 10.1016/j.jep.2024.118161. Epub 2024 Apr 9.

DOI:10.1016/j.jep.2024.118161
PMID:38599474
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood.

AIM OF THE STUDY

To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota.

MATERIALS AND METHODS

AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aβ. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments.

RESULTS

KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant.

CONCLUSION

KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.

摘要

民族药理学相关性

开心散(KXS)是一种用于治疗和预防阿尔茨海默病(AD)的经典中药方剂,疗效确切,但其作用机制涉及多个成分、途径和靶点,尚未完全明确。

研究目的

验证开心散对肠道微生物群的影响,并探讨其与肠道微生物群相关的抗AD机制。

材料与方法

通过腹腔注射D-半乳糖和双侧海马CA1区注射Aβ建立并评估AD大鼠模型。开心散在体内的药效学包括一般行为、莫里斯水迷宫试验、酶联免疫吸附测定、尼氏染色和苏木精-伊红染色以及免疫荧光。采用16S rRNA基因测序技术对肠道微生物群进行系统分析。通过粪便微生物群移植(FMT)实验验证肠道微生物群在开心散抗AD作用中的潜在作用。

结果

开心散可显著改善AD模型大鼠体内的认知障碍,减少神经元损伤,减轻神经炎症和结肠炎症。筛选出9种与AD相关的差异肠道细菌,其中4种细菌(鼠乳杆菌、 Ligilactobacillus、Alloprevotella、普雷沃氏菌科_NK3B31组)差异非常显著。

结论

开心散可维持肠道微生物群的生态平衡,并通过微生物群-肠-脑轴调节AD大鼠肠道微生物群的组成和比例,发挥其抗AD作用。

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