南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (9): 1867-1879.doi: 10.12122/j.issn.1673-4254.2025.09.07

• • 上一篇    

清肾颗粒通过调控miR-23b及Nrf2通路改善慢性肾脏病湿热证患者的肾功能:基于网络药理学和临床试验

呼琴1(), 金华2,3()   

  1. 1.安徽中医药大学第一临床医学院,安徽 合肥 230000
    2.合肥综合性国家科学中心大健康研究院//新安医学与中医药现代化研究所,安徽 合肥 230031
    3.安徽中医药大学第一附属医院肾内科,安徽 合肥 230031
  • 收稿日期:2025-03-27 出版日期:2025-09-20 发布日期:2025-09-28
  • 通讯作者: 金华 E-mail:qinhu992024@163.com;ya790312@sina.com
  • 作者简介:呼 琴,在读博士研究生,E-mail: qinhu992024@163.com
  • 基金资助:
    国家自然科学基金(82274307);合肥综合性国家科学中心大健康研究院新安医学与中医药现代化研究所专项资金(2023CXMMTCM018)

Qingshen Granules improves renal function of patients with chronic kidney disease damp-heat syndrome by activating the miR-23b and Nrf2 pathway

Qin HU1(), Hua JIN2,3()   

  1. 1.First Clinical Medical College of Anhui University of Chinese Medicine, Hefei 230000, China
    2.Institute of Xin'an Medicine and Modernization of Traditional Chinese Medicine, Institute of Health, Hefei Comprehensive National Science Center, Hefei 230031, China
    3.Department of Nephrology, First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China
  • Received:2025-03-27 Online:2025-09-20 Published:2025-09-28
  • Contact: Hua JIN E-mail:qinhu992024@163.com;ya790312@sina.com
  • Supported by:
    National Natural Science Foundation of China(82274307)

摘要:

目的 探讨清肾颗粒对慢性肾脏病(CKD)湿热证患者miR-23b及Nrf2通路及氧化应激干预作用。 方法 通过TCMSP、UniProt检索并映射清肾颗粒调控靶点,利用Small RNA测序技术筛选慢性肾衰竭湿热证的疾病基因,构建“活性成分-交集靶点-疾病”网络。利用KEGG通路富集分析及分子对接,明确清肾颗粒通过Nrf2通路影响CKD的靶点。临床试验:纳入60例CKD3~5期且表现为湿热证的非透析患者,设观察组和对照组,30例/组,另设20例正常组。对照组接受西医常规治疗,观察组在此基础上加用清肾颗粒,疗程8周。检测指标包括PBMC中miR-23b-5p、Nrf2和HO-1蛋白的表达水平,肾功能指标(Scr、eGFR),以及血清中ROS、AOPP、 PON-1的含量。 结果 清肾颗粒经筛选得到6种主要活性成分,10个关键靶点(ACTB、JUN、PTEN、ESR1、GSK3B、PPARG、PIK3CA、APP、PIK3R1、BECN1)。通过Small RNA测序,发现miR-23b-5p基因表达上调。KEGG通路分析显示Nrf2通路发挥重要作用。分子对接揭示核心靶点与活性成分结合活性良好,NFE2L2与木犀草素结合活性最好。清肾颗粒能降低患者血清Scr及ROS和AOPP水平,升高eGFR及血清PON-1水平(P<0.05);升高PBMC中的 Nrf2和HO-1蛋白水平(P<0.05);升高miR-23b-5p的表达水平(P<0.05)。 结论 miR-23b表达及Nrf2通路异常可能是CKD湿热证患者的关键干预靶点。清肾颗粒能通过多种活性成分作用于多靶点改善CKD湿热证患者肾功能,其治疗效果可能与 miR-23b 表达的上调、Nrf2 抗氧化通路活性的增强以及机体氧化应激水平的降低密切相关。

关键词: 清肾颗粒, 慢性肾脏病, microRNA, Nrf2通路, 网络药理学

Abstract:

Objective To investigate the therapeutic mechanism of Qingshen Granules (QSG) in patients with chronic kidney disease (CKD) damp-heat syndrome. Methods The regulatory targets of QSG were retrieved and mapped using TCMSP and UniProt. Small RNA sequencing technology was used to screen the target genes of chronic renal failure damp-heat syndrome to construct the "active ingredients-intersection targets-diseases" network, followed by KEGG pathway enrichment analysis and molecular docking of the core targets. Sixty patients with CKD (stage 3-5) presenting with damp-heat syndrome and not undergoing dialysis were randomized equally into two groups for conventional Western medicine treatment (control group) and additional treatment with QSG (observation group) for 8 weeks, with 20 healthy individuals as the normal control group. The expression levels of miR-23b-5p, Nrf2 and HO-1 protein in peripheral blood mononuclear cells (PBMC), renal function indicators (Scr and eGFR), and serum ROS, AOPP and PON-1 levels were compared among the 3 groups after the treatments. Results Six main active ingredients of QSG were identified, and their key targets included ACTB, JUN, PTEN, ESR1, GSK3B, PPARG, PIK3CA, APP, PIK3R1, and BECN1. MiR-23b-5p expression was significantly up-regulated in CKD damp-heat syndrome, in which the Nrf2 pathway abnormality played an important pathogenic role. Molecular docking results suggested good binding activity of the core targets with the active ingredients of QSG, and NFE2L2 had the strongest binding with luteolin. In patients with CKD damp-heat syndrome, QSG treatment significantly decreased serum Scr, ROS and AOPP levels, obviously improved eGFR, and increased serum PON-1 levels, expression levels of Nrf2 and HO-1 proteins in PBMCs, and the expression level of miR-23b-5p. Conclusion QSG can improve the renal function in patients with CKD damp-heat syndrome possibly by up-regulating miR-23b expression, activating the Nrf2 antioxidant pathway, and reducing oxidative stress levels.

Key words: Qingshen Granules, chronic kidney disease, microRNA, Nrf2 pathway, network pharmacology