Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Hefei 230031, China.
College of Pharmacy, Anhui university of Chinese Medicine, 103 Meishan Road, Hefei, China.
J Ethnopharmacol. 2016 Dec 4;193:140-149. doi: 10.1016/j.jep.2016.08.011. Epub 2016 Aug 4.
Chronic glomerulonephritis (CGN) is a primary glomerular disease that is related to immune-mediated inflammatory diseases. Qi Teng Xiao Zhuo granules have been proposed as a prescription of traditional Chinese medicine for treatment of CGN, but the comprehensive molecular mechanism underlying this therapeutic effect is not clear to date. The aim of this study was to evaluate and analyze the possible roles and molecular mechanisms of Qi Teng Xiao Zhuo granule-mediated treatment of CGN induced by adriamycin in rats.
For gene expression analysis, four samples of glomerular tissue from rats in the Qi Teng Xiao Zhuo granule group and four samples each from the adriamycin treated and control groups were hybridized with Agilent Rat 4×44K whole genome microarrays. KEGG and Gene Ontology (GO) analyses and LIMMA, String and Cytoscape software were used to analyze the functional microarray data and screen differentially expressed genes. Hub genes were identified using Pathway Studio software. Real-time PCR was performed to verify the selected genes.
Microarray gene expression analysis showed that Pnoc, Cacfd1, Fos, Igll1, Lcn2, and Syk were among the most downregulated genes in the Qi Teng Xiao Zhuo granule group compared with the adriamycin treated group, whereas Cyp2c7, Hsd3b6, Acsm5, and Ugt2b15 were significantly upregulated. Functional analysis demonstrated that metabolism of xenobiotics by cytochrome P450, the B cell receptor signaling pathway, and cytokine-cytokine receptor interaction pathways were significantly downregulated in the Qi Teng Xiao Zhuo granule group and that GO terms related to positive regulation of immune response, immune response-activating signal transduction, cell differentiation, cell cycle, proliferation, and adhesion were significantly affected. Fos and Syk were considered to be potential hub genes.
In the adriamycin-induced CGN rat model, comprehensive molecular mechanisms were involved with complex gene expression alterations containing many altered pathways and GO terms. However, how Qi Teng Xiao Zhuo granules regulate these events warrants further investigation.
慢性肾小球肾炎（CGN）是一种与免疫介导的炎症性疾病相关的原发性肾小球疾病。芪藤消浊颗粒已被提议作为治疗 CGN 的中药方剂，但迄今为止，其治疗效果的综合分子机制尚不清楚。本研究旨在评估和分析芪藤消浊颗粒治疗阿霉素诱导的 CGN 大鼠的可能作用和分子机制。
为了进行基因表达分析，从芪藤消浊颗粒组、阿霉素组和对照组的大鼠肾小球组织中各取 4 个样本进行杂交，使用 Agilent Rat 4×44K 全基因组微阵列进行杂交。使用 KEGG 和基因本体论（GO）分析以及 LIMMA、String 和 Cytoscape 软件分析功能微阵列数据并筛选差异表达基因。使用 Pathway Studio 软件识别枢纽基因。使用实时 PCR 验证所选基因。
微阵列基因表达分析显示，与阿霉素组相比，芪藤消浊颗粒组中 Pnoc、Cacfd1、Fos、Igll1、Lcn2 和 Syk 等基因表达下调最为显著，而 Cyp2c7、Hsd3b6、Acsm5 和 Ugt2b15 等基因表达上调最为显著。功能分析表明，芪藤消浊颗粒组细胞色素 P450 介导的外源性物质代谢、B 细胞受体信号通路和细胞因子-细胞因子受体相互作用通路显著下调，与免疫反应正向调节、免疫反应激活信号转导、细胞分化、细胞周期、增殖和黏附相关的 GO 术语也显著受到影响。Fos 和 Syk 被认为是潜在的枢纽基因。
在阿霉素诱导的 CGN 大鼠模型中，涉及复杂的基因表达改变，包含许多改变的途径和 GO 术语，涉及综合分子机制。然而，芪藤消浊颗粒如何调节这些事件需要进一步研究。
