The Second Central Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, China.
The Second Central Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, China.
Biomed Pharmacother. 2017 Sep;93:316-326. doi: 10.1016/j.biopha.2017.04.128. Epub 2017 Jun 24.
This study investigated the possible molecular mechanisms of pure total flavonoids from citrus (PTFC) for the treatment of non-alcoholic fatty liver disease (NAFLD) via toll-like receptor/C-C chemokine ligand (TLR/CCL) signaling pathways by monitoring the changes in gene expression profile in liver tissues induced by high-fat diet.
We performed systematical analyses on hepatic expression profiles of mRNAs in a high-fat diet (HFD)-induced steatotic animal model with or without PTFC treatment. The study was conducted by using MouseOneArray v2 gene chip, and analyzed by bioinformatics tools for differential gene expression. Real time-PCR, Western blot and liquid suspension array analysis were used to validate specific genes in the NAFLD liver expression profile in which PTFC plays a role in the TLR/CCR pathway.
We found that a total of 562 genes showed varying degrees of reversal after PTFC intervention. Pathway analysis of the differential gene expression in the HFD group and the normal diet group (ND group) revealed six signaling pathways related to inflammatory responses in the top ten results. Comparison of genes between the HFD+PTFC and the HFD groups indicated seven signaling pathways correlated with inflammatory response in the top ten results of the pathway analysis. The TLR/CCL inflammatory signaling pathways played an essential role during liver inflammation in NAFLD mice induced by high-fat diet. Real-time PCR, Western blot and liquid suspension array analysis of the differential gene expression involving the TLR/CCL signaling pathways validated the results of microarray detection.
PTFC may improve NAFLD by regulating TLR/CCL signaling pathways. Genomic studies provide additional evidence supporting the role of PTFC in the treatment of NAFLD.
本研究通过监测高脂饮食诱导的肝组织基因表达谱的变化，探讨柑橘总黄酮（PTFC）通过 Toll 样受体/C-C 趋化因子配体（TLR/CCL）信号通路治疗非酒精性脂肪性肝病（NAFLD）的可能分子机制。
我们对高脂饮食（HFD）诱导的脂肪变性动物模型中肝脏组织 mRNA 的表达谱进行了系统分析，观察有无 PTFC 治疗的变化。研究采用 MouseOneArray v2 基因芯片进行，通过生物信息学工具对差异表达基因进行分析。实时 PCR、Western blot 和液体悬浮阵列分析用于验证 TLR/CCR 通路中 PTFC 发挥作用的 NAFLD 肝表达谱中的特定基因。
我们发现，PTFC 干预后共有 562 个基因表现出不同程度的逆转。对 HFD 组和正常饮食组（ND 组）差异基因表达的通路分析显示，前 10 个结果中有 6 个与炎症反应相关的信号通路。HFD+PTFC 组与 HFD 组基因比较，通路分析前 10 个结果中有 7 个与炎症反应相关的信号通路。TLR/CCL 炎症信号通路在高脂肪饮食诱导的 NAFLD 小鼠肝脏炎症中起重要作用。TLR/CCL 信号通路差异基因表达的实时 PCR、Western blot 和液体悬浮阵列分析验证了微阵列检测的结果。
PTFC 可能通过调节 TLR/CCL 信号通路改善 NAFLD。基因组研究为 PTFC 治疗 NAFLD 的作用提供了额外的证据支持。
