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坦索罗辛对肝硬化大鼠模型肠道微生物群组成和肠道屏障功能的调节作用

Microbiota composition and intestinal barrier function modulated by tamsulosin and in a cirrhosis rat model.

作者信息

Padilla-García Silvia Valeria, Loera-Muro Abraham, Muñoz-Ortega Martín Humberto, Hernández-Marín David Alejandro, Ventura-Juárez Javier, Martínez-Hernández Sandra Luz

机构信息

Department of Morphology, Center for Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Ags, Mexico.

Secihti-Center for Biological Research of the Northwest, SC, La Paz, Mexico.

出版信息

Front Cell Infect Microbiol. 2025 Sep 2;15:1624065. doi: 10.3389/fcimb.2025.1624065. eCollection 2025.

Abstract

INTRODUCTION

The pathological progression of cirrhosis disrupts the gut-liver axis. () exhibits immunomodulatory properties and an ability to enhance intestinal barrier function. It has been demonstrated that tamsulosin has antifibrotic and anti-inflammatory effects in hepatic injury models. This study evaluated the effect of a tamsulosin and co-treatment on the recovery of microbiota and intestinal barrier integrity in a Wistar rat liver cirrhosis model.

MATERIAL AND METHODS

Male Wistar rats were administered CCl intraperitoneally for 4 weeks. Subsequently, rats received tamsulosin, , or both, orally for 2 weeks. The intestinal microbiota was assessed using 16S rRNA gene sequencing. Intestinal barrier integrity was evaluated using qPCR and Western blot for proteins ZO-1, occludin, and claudin-2. Bacterial translocation was evaluated by endotoxin concentration, bacterial DNA, and microbial culture of extraintestinal tissues. Finally, hepatic, intestinal histology, and liver function markers were analyzed.

RESULTS

and its combination with tamsulosin (T/) increased microbial diversity and promoted a balanced gut microbiota characterized by a predominance followed by and reduced and levels. group upregulated ZO-1 and occludin expression, while no significant changes were observed with tamsulosin or T/ groups, nonetheless, intestinal morphology resembled that of healthy controls. Bacterial translocation analysis revealed no endotoxins, bacterial DNA, or bacteria in extraintestinal tissues. Both treatments also improved hepatic and intestinal histology, with partial liver function recovery.

CONCLUSIÓN: Findings such as reduced bacterial translocation, lower systemic endotoxin levels, improved intestinal morphology, and modulation of gut microbiota composition suggest that both agents ( and tamsulosin), particularly in combination, exert positive effects on the intestinal barrier in cirrhosis.

摘要

引言

肝硬化的病理进展会破坏肠-肝轴。()具有免疫调节特性以及增强肠道屏障功能的能力。已有研究表明,坦索罗辛在肝损伤模型中具有抗纤维化和抗炎作用。本研究评估了坦索罗辛与()联合治疗对Wistar大鼠肝硬化模型中微生物群恢复和肠道屏障完整性的影响。

材料与方法

雄性Wistar大鼠腹腔注射四氯化碳4周。随后,大鼠口服坦索罗辛、()或两者联合用药2周。使用16S rRNA基因测序评估肠道微生物群。通过qPCR和蛋白质ZO-1、闭合蛋白和紧密连接蛋白-2的western印迹评估肠道屏障完整性。通过内毒素浓度、细菌DNA和肠外组织的微生物培养评估细菌移位。最后,分析肝脏、肠道组织学和肝功能指标。

结果

()及其与坦索罗辛的联合用药(T/)增加了微生物多样性,并促进了以()占优势、其次是()以及()和()水平降低为特征的肠道微生物群平衡。()组上调了ZO-1和闭合蛋白的表达,而坦索罗辛组或T/组未观察到显著变化,尽管如此,肠道形态与健康对照相似。细菌移位分析显示肠外组织中没有内毒素、细菌DNA或细菌。两种治疗方法还改善了肝脏和肠道组织学,部分肝功能得到恢复。

结论

细菌移位减少、全身内毒素水平降低、肠道形态改善以及肠道微生物群组成的调节等结果表明,两种药物(()和坦索罗辛),特别是联合使用时,对肝硬化患者的肠道屏障具有积极作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/745b/12436309/e80647c5dcd0/fcimb-15-1624065-g001.jpg

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