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槲皮素通过调节肠道菌群-SCFAs-炎症信号轴改善去卵巢大鼠的骨丢失。

Quercetin ameliorates bone loss in OVX rats by modulating the intestinal flora-SCFAs-inflammatory signaling axis.

机构信息

Department of Spine Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, Hubei Province 430074, PR China.

School of Sports Medicine, Wuhan Institute of Physical Education, Wuhan City, Hubei Province 430079, PR China.

出版信息

Int Immunopharmacol. 2024 Jul 30;136:112341. doi: 10.1016/j.intimp.2024.112341. Epub 2024 May 28.

DOI:10.1016/j.intimp.2024.112341
PMID:38810309
Abstract

BACKGROUND

Osteoporosis (OP) is a common systemic skeletal disorder characterized by an imbalance in bone homeostasis, involving increased osteoclastic bone formation and decreased osteoblastic bone resorption. Quercetin is a plant polyphenol that has been found to exhibit various biological activities, including antioxidant, anti-inflammatory, and antimicrobial effects. Previous studies have demonstrated its potential to improve postmenopausal OP, although the exact mechanism remains unclear. This study aims to investigate the anti-osteoporotic mechanism of quercetin based on the "intestinal flora - short-chain fatty acids (SCFAs) - inflammatory" signaling axis.

METHODS

In this study, we established an ovariectomized (OVX)-induced rat model, quercetin intervention and evaluated the effects on rats following antibiotic (ABX) treatment and fecal microbiota transplantation (FMT). After 6 weeks of intervention, the rats were euthanized, and samples from their femur, tibia, lumbar spine, serum, colon and feces were collected, and bone strength, intestinal flora structure, SCFAs levels and cytokine levels were assessed.

RESULTS

Quercetin modulates the intestinal flora by increasing potentially probiotic bacteria (i.e., Lactobacillales, Prevotellaceae, and Blautia) and decreasing potentially pathogenic bacteria (Desulfobacterota, Erysipelotrichales, Romboutsia, and Butyricoccaceae). It also increases SCFAs content and reduces colonic permeability by enhancing tight junction proteins (ZO-1, Occludin). Furthermore, quercetin lowers proinflammatory cytokine levels (LPS, IL-1β, and TNF-α), which enhances bone strength and prevents OVX-induced bone loss.

CONCLUSIONS

Quercetin may effectively reduce bone loss in OVX rats via the "intestinal flora - SCFAs - inflammatory" signaling pathway.

摘要

背景

骨质疏松症(OP)是一种常见的全身性骨骼疾病,其特征是骨稳态失衡,涉及破骨细胞骨形成增加和成骨细胞骨吸收减少。槲皮素是一种植物多酚,已被发现具有多种生物活性,包括抗氧化、抗炎和抗菌作用。先前的研究表明,它有可能改善绝经后 OP,尽管确切的机制尚不清楚。本研究旨在基于“肠道菌群-短链脂肪酸(SCFAs)-炎症”信号轴探讨槲皮素的抗骨质疏松机制。

方法

本研究建立了去卵巢(OVX)诱导的大鼠模型,进行槲皮素干预,并评估抗生素(ABX)治疗和粪便微生物群移植(FMT)后大鼠的效果。干预 6 周后,对大鼠进行安乐死,采集其股骨、胫骨、腰椎、血清、结肠和粪便样本,评估骨强度、肠道菌群结构、SCFAs 水平和细胞因子水平。

结果

槲皮素通过增加潜在的益生菌(即乳杆菌目、普雷沃氏菌科和 Blautia)和减少潜在的致病菌(脱硫杆菌门、肠杆菌目、Romboutsia 和丁酸球菌科)来调节肠道菌群。它还通过增强紧密连接蛋白(ZO-1、Occludin)增加 SCFAs 含量并降低结肠通透性。此外,槲皮素降低促炎细胞因子水平(LPS、IL-1β和 TNF-α),从而增强骨强度并防止 OVX 诱导的骨丢失。

结论

槲皮素可能通过“肠道菌群-SCFAs-炎症”信号通路有效减少 OVX 大鼠的骨丢失。

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