基于肠道菌群分析和网络药理学的新方法解释 L. 方改善大鼠高尿酸血症肾病作用机制。
A Novel Approach Based on Gut Microbiota Analysis and Network Pharmacology to Explain the Mechanisms of Action of L. Formula in the Improvement of Hyperuricemic Nephropathy in Rats.
机构信息
Immunotherapy Laboratory, College of Pharmacology, Southwest Minzu University, Chengdu, 610225, People's Republic of China.
Qinghai Tibet Plateau Research Institute, Southwest Minzu University, Chengdu, 610225, People's Republic of China.
出版信息
Drug Des Devel Ther. 2023 Jan 20;17:107-128. doi: 10.2147/DDDT.S389811. eCollection 2023.
BACKGROUND
L. formula (CILF) is a traditional Chinese medicine (TCM) widely used in the treatment of gout and hyperuricemic nephropathy (HN). The aim of this research was to investigate the potential protective effect of CILF against HN and elucidated the underlying mechanism.
METHODS
CILF water extract was administered to an HN rat model established by adenine combined with ethambutol. The levels of uric acid (UA), serum urea nitrogen (UREA), and creatinine (CREA) were detected. Changes in the pathology and histology of the kidney were observed by hematoxylin-eosin staining. The 16S rRNA of the gut microbiota was sequenced. The binding ability of the main ingredients of CILF to key targets was analyzed by network pharmacology and molecular docking. The expression levels of the related mRNAs and proteins in the kidney were evaluated by RT-qPCR and immunohistochemistry analysis.
RESULTS
CILF administration significantly alleviated increases in UA, UREA, and CREA, structural damage, and kidney dysfunction. Gut microbiota analysis was applied to explore the pharmacological mechanism of the effects of CILF on bacterial diversity and microbiota structure in HN. CILF decreased the abundance of . In addition, it increased the abundance of , and . Based on network pharmacology and molecular docking analysis, CILF profoundly influenced the IL17, TNF and AGE-RAGE signaling pathway. Additionally, CILF inhibited the expression of STAT3, VEGFA and SIRT1 to improve the symptoms of nephropathy. Our research suggested that CILF protects against kidney dysfunction in rats with HN induced by adenine combined with ethambutol.
CONCLUSION
Our findings on the anti-HN effects of CILF and its mechanism of action, from the viewpoint of systems biology, and elaborated that CILF can alter the diversity and community structure of the gut microbiota in HN, providing new approaches for the prevention and treatment of HN.
背景
L. formula（CILF）是一种广泛用于治疗痛风和高尿酸血症肾病（HN）的中药。本研究旨在探讨 CILF 对 HN 的潜在保护作用，并阐明其潜在机制。
方法
用腺嘌呤联合乙胺丁醇建立 HN 大鼠模型，给予 CILF 水提取物。检测尿酸（UA）、血清尿素氮（UREA）和肌酐（CREA）水平。通过苏木精-伊红染色观察肾脏病理和组织学变化。对肠道微生物群的 16S rRNA 进行测序。通过网络药理学和分子对接分析 CILF 主要成分与关键靶点的结合能力。通过 RT-qPCR 和免疫组织化学分析评估肾脏相关 mRNA 和蛋白的表达水平。
结果
CILF 给药可显著减轻 UA、UREA 和 CREA 升高、结构损伤和肾功能障碍。应用肠道微生物群分析探讨 CILF 对 HN 细菌多样性和微生物群结构影响的药理机制。CILF 降低了 的丰度。此外，它增加了 的丰度。基于网络药理学和分子对接分析，CILF 显著影响了 IL17、TNF 和 AGE-RAGE 信号通路。此外，CILF 抑制了 STAT3、VEGFA 和 SIRT1 的表达，改善了肾病症状。我们的研究表明，CILF 可预防腺嘌呤联合乙胺丁醇诱导的 HN 大鼠肾功能障碍。
结论
从系统生物学的角度出发，我们对 CILF 抗 HN 作用及其作用机制的研究表明，CILF 可以改变 HN 中肠道微生物群的多样性和群落结构，为 HN 的防治提供了新的方法。
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