Luo Yan, Xuan Chen, Cheng Junxiong, Xiong Yu, Cao Wenfu
College of Traditional Chinese Medicine, Chongqing Medical University, Department of Chinese Traditional Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Department of Chinese Traditional Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China.
Evid Based Complement Alternat Med. 2022 May 25;2022:4194827. doi: 10.1155/2022/4194827. eCollection 2022.
Dahuang and Huangqi are the most frequently prescribed treatment methods for chronic kidney disease in China. Our study aimed to clarify the pharmacological mechanism of action of Dahuang-Huangqi decoction (DHHQD) in renal interstitial fibrosis (RIF). The intersection of genes targeted by DHHQD active ingredients and RIF target genes was searched using network pharmacology to build a chemical ingredient and disease target network. For analysis, Sprague-Dawley rats with unilateral urethral obstruction (UUO) were administered DHHQD, and their kidney function-related indicators and pathological indices were determined. The expression of core targets was quantified using real-time polymerase chain reaction and western blotting. A total of 139 common targets for DHHQD and RIF in chronic kidney disease were detected. Compared with the untreated UUO rats, the DHHQD-treated rats showed reductions in the following: blood urea nitrogen and serum creatinine levels, kidney tubular atrophy and necrosis, interstitial fibrosis, hyperplasia and abnormal deposition of extracellular matrix, and microstructural changes in the mesangial matrix and glomerular basement membrane. DHHQD treatment significantly regulated the levels of renal core proteins, such as eNOS, IL-6, EGFR, and VEGF and reduced the mRNA and protein expression of the core targets involved in inflammation pathways, such as PI3K/AKT and TLR4/NF-B. DHHQD treatment ameliorated the severity of RIF by potentially regulating the AKT/PI3K and TLR4/NF-B signaling pathways. Our study findings provide insights into the mechanisms associated with DHHQD action and essential data for future research.
大黄和黄芪是中国慢性肾脏病最常用的治疗方法。我们的研究旨在阐明大黄-黄芪汤（DHHQD）在肾间质纤维化（RIF）中的药理作用机制。利用网络药理学搜索DHHQD活性成分靶向基因与RIF靶基因的交集，构建化学成分与疾病靶点网络。为了进行分析，对单侧输尿管梗阻（UUO）的Sprague-Dawley大鼠给予DHHQD，并测定其肾功能相关指标和病理指标。使用实时聚合酶链反应和蛋白质印迹法定量核心靶点的表达。共检测到慢性肾脏病中DHHQD和RIF的139个共同靶点。与未治疗的UUO大鼠相比，DHHQD治疗的大鼠在以下方面有所降低：血尿素氮和血清肌酐水平、肾小管萎缩和坏死、间质纤维化、细胞外基质增生和异常沉积，以及系膜基质和肾小球基底膜的微观结构变化。DHHQD治疗显著调节了肾核心蛋白的水平，如eNOS、IL-6、EGFR和VEGF，并降低了参与炎症途径的核心靶点的mRNA和蛋白表达，如PI3K/AKT和TLR4/NF-κB。DHHQD治疗可能通过调节AKT/PI3K和TLR4/NF-κB信号通路改善RIF的严重程度。我们的研究结果为DHHQD作用机制提供了见解，并为未来研究提供了重要数据。
