黄芪汤对大鼠肝纤维化的作用：基因表达谱分析

Actions of Huangqi decoction against rat liver fibrosis: a gene expression profiling analysis.

作者信息

Zhang Gui-Biao, Song Ya-Nan, Chen Qi-Long, Dong Shu, Lu Yi-Yu, Su Ming-Yu, Liu Ping, Su Shi-Bing

机构信息

Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 China.

Liver Disease Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 China.

出版信息

Chin Med. 2015 Dec 18;10:39. doi: 10.1186/s13020-015-0066-5. eCollection 2015.

BACKGROUND

Huangqi decoction (HQD) is used for liver fibrosis and cirrhosis treatment in Chinese medicine. This study aims to investigate the pharmacological actions of HQD against liver fibrosis in rats by high-throughput gene expression profiling, network analysis and real-time qRT-PCR.

METHODS

We analyzed the profiles of differentially expressed genes (DEGs) in dimethylnitrosamine (DMN)-induced liver fibrosis in rat. The liver tissue samples of control group (n = 3), model group (n = 3) and HQD group (n = 3) were examined by microarrays. Pathways were analyzed by KEGG. Pathway-gene and protein-protein interaction (PPI) networks were constructed with Cytoscape software. The expression of candidate genes was verified by qRT-PCR. P values less than 0.05 indicated statistical significance.

RESULTS

Collagen deposition and hydroxyproline (Hyp) content were decreased in the HQD group compared with the model group (P < 0.001), while that of Hyp in the model group were increased compared with the control group (P < 0.001). In comparison with the model group, 1085 DEGs (all P < 0.05, |fold change| >1.5) and 52 pathways in the HQD group were identified. TGF-beta, ECM-receptor interaction, and the cell adhesion molecules pathways were significantly recovered by HQD (P < 0.001). A pathway-gene network was constructed, including 303 DEGs and 52 pathways, and 514 nodes and 2602 edges, among 142 genes with node degrees greater than 10. The expressions of PDGFra, PDGFrb, PDGFb, PDGFd, COL1A1, COL1A2, COL5A2, and THBS1 were significantly down-regulated by HQD (P < 0.001).

CONCLUSION

HQD down-regulated the expressions of PDGFra, PDGFrb, PDGFb, PDGFd, COL1A1, COL1A2, COL5A2 and THBS1, and TGF-β and PDGF signaling pathways in the DMN-induced liver fibrosis in rats.

背景

在中医中，黄芪汤（HQD）用于治疗肝纤维化和肝硬化。本研究旨在通过高通量基因表达谱分析、网络分析和实时定量逆转录聚合酶链反应（qRT-PCR）研究HQD对大鼠肝纤维化的药理作用。

方法

我们分析了二甲基亚硝胺（DMN）诱导的大鼠肝纤维化中差异表达基因（DEG）的谱。通过微阵列检测对照组（n = 3）、模型组（n = 3）和HQD组（n = 3）的肝组织样本。通过京都基因与基因组百科全书（KEGG）分析通路。使用Cytoscape软件构建通路-基因和蛋白质-蛋白质相互作用（PPI）网络。通过qRT-PCR验证候选基因的表达。P值小于0.05表示具有统计学意义。

结果

与模型组相比，HQD组的胶原沉积和羟脯氨酸（Hyp）含量降低（P < 0.001），而模型组的Hyp含量与对照组相比增加（P < 0.001）。与模型组相比，HQD组鉴定出1085个DEG（所有P < 0.05，|倍数变化| > 1.5）和52条通路。HQD显著恢复了转化生长因子-β（TGF-β）、细胞外基质受体相互作用和细胞粘附分子通路（P < 0.001）。构建了一个通路-基因网络，包括303个DEG和52条通路，以及514个节点和2602条边，其中142个基因的节点度大于10。HQD显著下调了血小板衍生生长因子受体α（PDGFra）、血小板衍生生长因子受体β（PDGFrb）、血小板衍生生长因子B（PDGFb）、血小板衍生生长因子D（PDGFd）、Ⅰ型胶原蛋白α1（COL1A1）、Ⅰ型胶原蛋白α2（COL1A2）、Ⅴ型胶原蛋白α2（COL5A2）和血小板反应蛋白1（THBS1）的表达（P < 0.001）。