通腑醒参胶囊通过调节肠道菌群和鞘脂代谢减轻脑卒中相关肺炎多器官损伤

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-04-12 DOI:10.1016/j.phymed.2025.156756

Ruihua Wang , Changlian Gan , Baoying Gong , Juan Huang , Zhenzhen Lou , Daxiu Wang , Ru Yan , Geng Li , Tianqin Xiong , Jianwen Guo

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引用次数: 0

摘要

脑卒中相关性肺炎（SAP）是脑出血（ICH）患者的主要并发症和死亡原因。迫切需要开发更有效的治疗策略。通腑醒神胶囊（TFXS）是一种用于治疗脑出血和SAP的中药，但其作用机制尚未完全阐明。目的采用吸入诱导肺炎克雷伯菌感染合并脑出血大鼠模型和气管内注射脂多糖（LPS）诱导急性肺损伤合并脑出血大鼠模型，探讨TFXS对SAP的治疗作用及机制。方法采用ULPLC-Q萃取-轨道谱联用技术对TFXS的化学成分进行表征。通过神经学评分、组织病理学分析、磁共振成像、免疫荧光、阿利新蓝核快红染色、髓过氧化物酶活性评估、白细胞计数、ELISA等方法评价TFXS的治疗效果。为了研究潜在的机制，进行了粪便微生物群移植、16S rRNA测序、非靶向代谢组学和Spearman相关分析。结果共鉴定出60个化合物。药理分析显示，TFXS通过减少白细胞和淋巴细胞的浸润，抑制中性粒细胞的浸润和过度活化，显著减轻神经功能缺损，增强血肿吸收，减轻脑损伤和神经炎症，改善肺炎和肺损伤。TFXS还通过增加酸性粘蛋白和紧密连接蛋白zonula occludens-1 （ZO-1）的表达，减轻肠道病变和屏障损伤。机制上，TFXS以肠道菌群依赖的方式改善肺炎和肺损伤。它通过调节sap诱导的肠道菌群失调和提高益生菌（包括乳酸杆菌、异源菌和肠球菌）的丰度，逆转鞘脂代谢紊乱和神经酰胺积累。结论tfxs通过缓解肠道菌群失调和鞘脂代谢紊乱，对脑、肺、肠道具有抗炎和保护作用。这些发现突出了TFXS作为治疗SAP的有希望的治疗候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Tongfu Xingshen capsule alleviates stroke-associated pneumonia-induced multiple organ injuries by modulating the gut microbiota and sphingolipid metabolism

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Tongfu Xingshen capsule alleviates stroke-associated pneumonia-induced multiple organ injuries by modulating the gut microbiota and sphingolipid metabolism

Background

Stroke-associated pneumonia (SAP) represents a major complication and cause of death in patients suffering from intracerebral haemorrhage (ICH). It's urgent to develop more effective therapeutic strategies. Tongfu Xingshen capsule (TFXS) is a traditional Chinese medicine that has been utilised in clinical studies for the treatment of ICH and SAP, but the underlying mechanisms remain to be fully elucidated.

Purpose

This study aims to explore the therapeutic effects and mechanisms of TFXS on SAP using an aspiration-induced Klebsiella pneumoniae infection-complicating ICH rat model and an intratracheal injection of lipopolysaccharide (LPS)-induced acute lung injury-complicating ICH rat model.

Methods

The chemical components of TFXS are characterised using ULPLC-Q Exactive-Orbitrap-MS. The therapeutic effects of TFXS are evaluated through neurological scoring, histopathology analysis, magnetic resonance imaging, immunofluorescence, Alcian blue-nuclear fast red staining, myeloperoxidase activity assessment, leukocyte counting, and ELISA. To investigate the underlying mechanisms, faecal microbiota transplantation, 16S rRNA sequencing, untargeted metabolomics, and Spearman correlation analyses are performed.

Results

A total of 60 compounds are identified in TFXS. Pharmacological analysis reveals that TFXS significantly mitigates neurological deficits, enhances haematoma absorption, attenuates brain damage and neuroinflammation, and improves pneumonia and pulmonary injury by reducing the infiltration of leukocytes and lymphocytes, as well as suppressing the infiltration and overactivation of neutrophils. TFXS also alleviates intestinal lesions and barrier damage by increasing acidic mucins and the expression of the tight junction protein zonula occludens-1 (ZO-1). Mechanistically, TFXS ameliorates pneumonia and pulmonary injury in a gut microbiota-dependent manner. It reverses sphingolipid metabolism disorders and ceramide accumulation by modulating SAP-induced gut microbiota dysbiosis and enhancing the abundance of probiotics, including Lactobacillus, Allobaculum and Enterococcus.

Conclusion

TFXS exerts anti-inflammatory and protective effects on the brain, lung, and gut by alleviating gut microbiota dysbiosis and sphingolipid metabolism disorders. These findings highlight TFXS as a promising therapeutic candidate for the treatment of SAP.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.