肾病II汤通过调节TLR4和肠道菌群沿肠肾轴减轻肾纤维化。

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Chen Liu, Yujiu Gao, Yirui Chen, Liting Zhu, Fu Rao, Yuhan Huang, Yini Zeng, Rui Cai, Fangyan Wang, Jinguo Cheng
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引用次数: 0

摘要

肾病II汤(NED)是一种广泛应用于治疗慢性肾脏疾病(CKD)的中药配方。尽管其广泛应用,其治疗效果的确切机制仍然知之甚少。本研究旨在阐明NED在减轻肾纤维化中的作用,并探讨其对肠肾轴的影响。采用超高效液相色谱-串联质谱(UPLC-MS/MS)对NED的主要成分进行分析。采用双侧肾缺血再灌注损伤(bIRI)模型诱导纤维化。RT-qPCR检测toll样受体4 (TLR4)、髓样分化因子88 (MyD88)、核因子-κB (NF-κB)信号通路相关mRNA的表达。Western blotting分析肾纤维化标志物、TLR4/MyD88/NF-κB通路蛋白、结肠蛋白ZO-1和Occludin-1的变化。采用酶联免疫吸附法(ELISA)定量测定血清尿毒症毒素水平,并进行16S核糖体RNA (rRNA)基因测序,探讨小鼠肠道微生物组的变化。我们的研究表明,NED组小鼠血清肌酐、血尿素氮和尿蛋白水平降低,同时肾脏损伤改善,肾纤维化标志物减少。bIRI组TLR4/MyD88/NF-κB蛋白和mRNA水平以及肠道紧密连接蛋白和肠源性尿毒症毒素水平均显著降低。NED治疗逆转了这些变化并改变了肠道微生物群。此外,粪便微生物移植(FMT)减轻了bIRI小鼠的肾脏损伤和纤维化。综上所述,NED通过调节肠道微生物群改善肾损伤和纤维化,并可能通过抑制TLR4表达进一步减轻纤维化,从而影响肠肾轴。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Nephropathy II Decoction Attenuates Renal Fibrosis via Regulating TLR4 and Gut Microbiota Along the Gut-Kidney Axis.

Nephropathy II Decoction (NED) is a widely used Chinese medicinal formulation for managing chronic kidney disease (CKD). Despite its extensive application, the precise mechanisms underlying its therapeutic effects remain poorly understood. This study aims to elucidate the role of NED in attenuating renal fibrosis and to explore its impact on the gut-kidney axis. The principal constituents of NED were analyzed using ultra-performance LC-tandem mass spectrometry (UPLC-MS/MS). A bilateral renal ischemia-reperfusion injury (bIRI) model was employed to induce fibrosis. RT-qPCR was utilized to assess the expression of mRNA related to the toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) and nuclear factor-κB (NF-κB) signaling pathway. Western blotting analysis was performed to identify changes in renal fibrosis markers, TLR4/MyD88/NF-κB pathway proteins, and the colon proteins ZO-1 and Occludin-1. Serum levels of uremic toxins were quantified using enzyme-linked immunosorbent assay (ELISA), and 16S ribosomal RNA (rRNA) gene sequencing was conducted to explore changes in the gut microbiome of the mice. Our study demonstrated that mice in the NED group exhibited reduced serum creatinine, blood urea nitrogen, and urinary protein levels, alongside improvements in kidney damage and a decrease in renal fibrosis markers. In the bIRI group, TLR4/MyD88/NF-κB protein and mRNA levels, as well as intestinal tight junction proteins and enterogenic uremic toxins, were significantly reduced. NED treatment reversed these changes and modified the gut microbiota. Furthermore, fecal microbial transplantation (FMT) alleviated kidney damage and fibrosis in bIRI mice. In summary, NED ameliorates kidney injury and fibrosis by modulating the gut microbiota and may further attenuate fibrosis through the inhibition of TLR4 expression, thereby influencing the gut-kidney axis.

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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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