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菊粉通过改善载脂蛋白E基因敲除小鼠的脂质代谢、炎症和肠道微生物群来减轻动脉粥样硬化:短链菊粉更有效。

Inulin alleviates atherosclerosis through improving lipid metabolism, inflammation, and gut microbiota in ApoE-knockout mice: the short-chain is more efficacious.

作者信息

Zhang Kun, Zeng Yu, Li Jiawei, Huang Yingchun, Zhang Nan, Gong Yue, Xiao Kaihu, Chen Jian, Chen Tiantian, Qiu Haomin, Lei Sisi, Yan Fei, Lang Chunhui, Duan Xudong, Dong Xianwen

机构信息

Chongqing University Three Gorges Hospital, Chongqing Municipality Clinical Research Center for Geriatric Diseases, Chongqing, China.

School of Medicine, Chongqing University, Chongqing, China.

出版信息

Front Pharmacol. 2024 Oct 10;15:1445528. doi: 10.3389/fphar.2024.1445528. eCollection 2024.

DOI:10.3389/fphar.2024.1445528
PMID:39449970
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11499155/
Abstract

INTRODUCTION

Atherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness. Therefore, this study aimed to investigate the effects and mechanisms of short-chain and long-chain inulin in AS.

METHODS

ApoE mice fed a high fat diet (HFD) were used to establish an atherosclerosis model. These mice received daily oral administration of either short-chain or long-chain inulin for 12 weeks. Plasma lipid metabolism-related indices were measured using biochemical analysis, and plasma immunological indices were analyzed via ELISA. The aorta, aortic root regions, liver tissue, adipose tissue, and colon tissue were examined through various staining techniques, including ORO staining, hematoxylin and eosin staining, Alcian blue staining, and immunofluorescent or immunohistochemical assays. Microbiome analysis was conducted in the cecal content.

RESULTS

The results indicated that both short-chain and long-chain inulin substantially reduced the formation of atherosclerotic plaques. Inulin also improved plasma lipid concentrations and hepatic lipid metabolism, and partially alleviated both localized (atherosclerotic lesions) and systemic inflammation. Short-chain inulin was more effective than long-chain inulin in reducing atherosclerotic plaques formation, enhancing lipid metabolism and reducing inflammation. Additionally, both types of inulin showed similar effectiveness in enhancing intestinal epithelial barrier integrity, gut microbiota composition and functionality.

CONCLUSION

These findings suggest that inulin has a protective role against atherosclerosis by enhancing lipid metabolism, reducing inflammation, and improving intestinal barrier and gut microbiota. As a dietary intervention, short-chain inulin is more effective than long-chain inulin, offering clinical implications for using inulin as a therapeutic agent for atherosclerosis.

摘要

引言

动脉粥样硬化(AS)被认为是许多疾病的根本原因,尤其是心血管和脑血管疾病。菊粉作为一种果聚糖,尽管存在相互矛盾的研究结果,但已显示出改善动脉粥样硬化的潜力。据推测,菊粉的聚合度可能在很大程度上影响其治疗效果。因此,本研究旨在探讨短链和长链菊粉对AS的影响及其机制。

方法

采用喂食高脂饮食(HFD)的载脂蛋白E基因敲除小鼠建立动脉粥样硬化模型。这些小鼠每天口服短链或长链菊粉,持续12周。使用生化分析测量血浆脂质代谢相关指标,并通过酶联免疫吸附测定(ELISA)分析血浆免疫指标。通过多种染色技术检查主动脉、主动脉根部区域、肝脏组织、脂肪组织和结肠组织,包括油红O染色、苏木精-伊红染色、阿尔辛蓝染色以及免疫荧光或免疫组织化学检测。对盲肠内容物进行微生物组分析。

结果

结果表明,短链和长链菊粉均能显著减少动脉粥样硬化斑块的形成。菊粉还改善了血浆脂质浓度和肝脏脂质代谢,并部分减轻了局部(动脉粥样硬化病变)和全身炎症。在减少动脉粥样硬化斑块形成、增强脂质代谢和减轻炎症方面,短链菊粉比长链菊粉更有效。此外,两种类型的菊粉在增强肠道上皮屏障完整性、肠道微生物群组成和功能方面显示出相似的效果。

结论

这些发现表明,菊粉通过增强脂质代谢、减轻炎症以及改善肠道屏障和肠道微生物群对动脉粥样硬化具有保护作用。作为一种饮食干预措施,短链菊粉比长链菊粉更有效,这为将菊粉用作动脉粥样硬化的治疗药物提供了临床启示。

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