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姜黄素缓解腹主动脉瘤进展的肠道微生物群多样性与代谢组学分析

Gut microbiota diversity and metabolomics analysis of curcumin's alleviation of abdominal aortic aneurysm progression.

作者信息

Cheng Shuai, Hao Xinyu, Wang Lei, Jiang Bo, Xin Shijie

机构信息

Department of Vascular and Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning Province, China.

Key Laboratory of Pathogenesis, Prevention, and Therapeutics of Aortic Aneurysm in Liaoning Province, Shenyang, Liaoning Province, China.

出版信息

Mol Cell Biochem. 2025 Jun 17. doi: 10.1007/s11010-025-05314-y.

DOI:10.1007/s11010-025-05314-y
PMID:40524097
Abstract

Abdominal aortic aneurysm (AAA) is a high-risk vascular condition with a significant need for effective treatments to slow its progression, particularly for small-diameter AAAs. While previous studies have demonstrated curcumin's beneficial effects in AAA mouse models, the role of gut microbiota homeostasis and metabolic changes in this context remains poorly understood. We developed a recently established AAA mouse model and assessed alterations in the gut microbiota. We also examined the effect of curcumin on AAA progression. Fecal samples from different groups of mice were collected and analyzed using 16 s rRNA sequencing to explore the role of gut microbiota in curcumin's therapeutic actions, while serum samples were analyzed by LC-MS/MS to investigate metabolic changes associated with curcumin's therapeutic effects. In a mouse AAA model induced by elastase periadventitial incubation combined with β-aminopropionitrile (BAPN), we observed reduced gut microbiota diversity and a decrease in several probiotic genera. Curcumin treatment inhibited AAA progression, reduced pathological aortic changes and downregulated the expression of pro-inflammatory cytokines. Additionally, curcumin prevented the phenotypic shift of vascular smooth muscle cells from a contractile to a synthetic state. Notably, curcumin improved gut microbiota diversity, increased probiotic genera abundance. Finally, curcumin modulated the serum metabolic profile, alleviating AAA-related metabolic changes. Curcumin enhances gut microbiota homeostasis, modulates metabolic changes, and inhibits AAA progression, offering new insights into its therapeutic potential for AAA management.

摘要

腹主动脉瘤(AAA)是一种高危血管疾病,迫切需要有效的治疗方法来减缓其进展,尤其是对于小直径腹主动脉瘤。虽然先前的研究已经证明姜黄素在腹主动脉瘤小鼠模型中具有有益作用,但在这种情况下肠道微生物群稳态和代谢变化的作用仍知之甚少。我们建立了一种最近建立的腹主动脉瘤小鼠模型,并评估了肠道微生物群的变化。我们还研究了姜黄素对腹主动脉瘤进展的影响。收集不同组小鼠的粪便样本,使用16s rRNA测序进行分析,以探讨肠道微生物群在姜黄素治疗作用中的作用,同时通过液相色谱-串联质谱法(LC-MS/MS)分析血清样本,以研究与姜黄素治疗效果相关的代谢变化。在通过弹性蛋白酶外膜周围孵育联合β-氨基丙腈(BAPN)诱导的小鼠腹主动脉瘤模型中,我们观察到肠道微生物群多样性降低以及几种益生菌属减少。姜黄素治疗抑制了腹主动脉瘤的进展,减少了主动脉的病理变化,并下调了促炎细胞因子的表达。此外,姜黄素阻止了血管平滑肌细胞从收缩状态向合成状态的表型转变。值得注意的是,姜黄素改善了肠道微生物群多样性,增加了益生菌属的丰度。最后,姜黄素调节了血清代谢谱,减轻了与腹主动脉瘤相关的代谢变化。姜黄素增强肠道微生物群稳态,调节代谢变化,并抑制腹主动脉瘤进展,为其在腹主动脉瘤治疗中的潜在应用提供了新的见解。

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本文引用的文献

1
Correlation analysis of the impact of juvenile on gut microbiota and transcriptome in mice.幼年对小鼠肠道微生物群和转录组影响的相关性分析
Microbiol Spectr. 2025 Feb 4;13(2):e0155024. doi: 10.1128/spectrum.01550-24. Epub 2024 Dec 27.
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2-Hydroxyisobutyric acid targeted binding to MT-ND3 boosts mitochondrial respiratory chain homeostasis in hippocampus to rescue diabetic cognitive impairment.2-羟基异丁酸靶向结合MT-ND3可增强海马体中的线粒体呼吸链稳态,以挽救糖尿病认知障碍。
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Curcumin suppresses colorectal tumorigenesis through restoring the gut microbiota and metabolites.
姜黄素通过恢复肠道微生物群和代谢物来抑制结直肠肿瘤发生。
BMC Cancer. 2024 Sep 12;24(1):1141. doi: 10.1186/s12885-024-12898-z.
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alleviates abdominal aortic aneurysms via restoring CITED2 activated by EPAS1.通过恢复 EPAS1 激活的 CITED2 缓解腹主动脉瘤。
Infect Immun. 2024 Oct 15;92(10):e0017224. doi: 10.1128/iai.00172-24. Epub 2024 Aug 29.
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Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study.肠道微生物群、血浆代谢物、炎症细胞因子与腹主动脉瘤之间的因果关系:一项孟德尔随机研究。
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Liraglutide attenuates angiotensin II-induced aortic dissection and aortic aneurysm via inhibiting M1 macrophage polarization in APOE mice.利拉鲁肽通过抑制 APOE 小鼠中 M1 巨噬细胞极化来减轻血管紧张素 II 诱导的主动脉夹层和腹主动脉瘤。
Biochem Pharmacol. 2024 May;223:116170. doi: 10.1016/j.bcp.2024.116170. Epub 2024 Mar 26.
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Branched-chain amino acid catabolic defect in vascular smooth muscle cells drives thoracic aortic dissection via mTOR hyperactivation.分支链氨基酸代谢缺陷导致血管平滑肌细胞中的 mTOR 过度激活,进而引发胸主动脉夹层。
Free Radic Biol Med. 2024 Jan;210:25-41. doi: 10.1016/j.freeradbiomed.2023.11.002. Epub 2023 Nov 11.
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Single-cell RNA sequencing reveals the vascular smooth muscle cell phenotypic landscape in aortic aneurysm.单细胞 RNA 测序揭示了腹主动脉瘤中血管平滑肌细胞的表型景观。
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Impact of in patients with abdominal aortic aneurysm: a cross-sectional study.腹主动脉瘤患者中[具体因素]的影响:一项横断面研究。 (你提供的原文中“of”后面缺少具体内容)
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Signaling through the IL-6-STAT3 Pathway Promotes Proteolytically-Active Macrophage Accumulation Necessary for Development of Small AAA.通过 IL-6-STAT3 通路的信号转导促进了蛋白水解活性的巨噬细胞的积累,这对于小 AAA 的发展是必要的。
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