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肠道微生物群的耗竭会削弱归肾丸在恢复小鼠卵巢功能及卵巢组织相关蛋白表达方面的有益作用。

The depletion of gut microbiome impairs the beneficial effect of Gui-Shen-Wan in restoring mice ovarian function and associated protein expression of ovarian tissues.

作者信息

Huang Xingtao, Xu Ruinan, Yang Qin, Jiang Xin, Lin Jinju, Zhao Huashan, Wu Ruifang, Du Hui, Dai Wenkui

机构信息

Department of Traditional Chinese Medicine, Peking University Shenzhen Hospital, Shenzhen, China.

Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China.

出版信息

Front Cell Infect Microbiol. 2024 Nov 27;14:1505958. doi: 10.3389/fcimb.2024.1505958. eCollection 2024.

DOI:10.3389/fcimb.2024.1505958
PMID:39664494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11632464/
Abstract

INTRODUCTION

Traditional Chinese Medicine (TCM), specifically Gui-Shen-Wan, has shown promise in restoring ovarian function among reproductive-age women who had impaired ovarian functions, yet the underlying mechanisms remain elusive. Recent studies highlight the pivotal role of the gut microbiome (GM) in mediating the therapeutic effects of TCM. However, it is unclear whether the GM contributes to Gui-Shen-Wan's therapeutic restoration of ovarian functions.

METHODS

This study employed a mouse model with cyclophosphamide-induced decreased ovarian function (P_T and P_AT groups) and a control group without modeling. The P_AT group received a 7-day course of oral antibiotics to deplete the GM prior to a 20-day Gui-Shen-Wan treatment regimen.

RESULTS

Both P_T and P_AT mice exhibited prolonged metestrus/diestrus phases compared to controls (p<0.05), indicating menstrual disruption post-modeling. Following 20 days of Gui-Shen-Wan treatment, P_T mice showed a shorter metestrus/diestrus phase (4 days) compared to P_AT mice (5 days) (p<0.05). Notably, P_T mice had a higher number of normal follicles(primitive/primary/secondary/antral follicles) in their ovaries post-treatment (median 15) compared to P_AT mice (median 8.5). Proteome analysis revealed that ovarian proteins enriched in P_T mice were primarily associated with oxidative phosphorylation and DNA replication pathways, suggesting GM-mediated enhancement of these processes.

DISCUSSION

This study underscores the pivotal role of the GM in the therapeutic benefits of Gui-Shen-Wan, highlighting the potential for microbiome-targeted interventions in promoting beneficial effects of Gui-Shen-Wan on the restoration of decreased ovarian functions.

摘要

引言

传统中医(TCM),特别是归肾丸,在恢复卵巢功能受损的育龄妇女的卵巢功能方面显示出前景,但其潜在机制仍不清楚。最近的研究强调了肠道微生物群(GM)在介导中医治疗效果中的关键作用。然而,尚不清楚GM是否有助于归肾丸对卵巢功能的治疗性恢复。

方法

本研究采用环磷酰胺诱导卵巢功能减退的小鼠模型(P_T组和P_AT组)以及未建模的对照组。P_AT组在进行为期20天的归肾丸治疗方案之前接受了为期7天的口服抗生素疗程以耗尽GM。

结果

与对照组相比,P_T组和P_AT组小鼠的动情后期/间情期均延长(p<0.05),表明建模后月经紊乱。归肾丸治疗20天后,P_T组小鼠的动情后期/间情期(4天)比P_AT组小鼠(5天)短(p<0.05)。值得注意的是,与P_AT组小鼠(中位数8.5)相比,P_T组小鼠治疗后卵巢中的正常卵泡(原始/初级/次级/窦状卵泡)数量更多(中位数15)。蛋白质组分析显示,P_T组小鼠中富集的卵巢蛋白主要与氧化磷酸化和DNA复制途径相关,表明GM介导了这些过程的增强。

讨论

本研究强调了GM在归肾丸治疗益处中的关键作用,突出了针对微生物群的干预措施在促进归肾丸对卵巢功能减退恢复的有益作用方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138b/11632464/c9f26c104b80/fcimb-14-1505958-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138b/11632464/15c8a002d2c9/fcimb-14-1505958-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138b/11632464/89c1d4f5d169/fcimb-14-1505958-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138b/11632464/599cda98b782/fcimb-14-1505958-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138b/11632464/c9f26c104b80/fcimb-14-1505958-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138b/11632464/15c8a002d2c9/fcimb-14-1505958-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138b/11632464/89c1d4f5d169/fcimb-14-1505958-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138b/11632464/599cda98b782/fcimb-14-1505958-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/138b/11632464/c9f26c104b80/fcimb-14-1505958-g004.jpg

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