Wu Aiming, Lou Lixia, Zhai Jianying, Zhang Dongmei, Chai Limin, Nie Bo, Zhu Haiyan, Gao Yonghong, Shang Hongcai, Zhao Mingjing
Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China.
National Engineering Research Center for R&D of TCM Multi-ingredient Drugs, Beijing 100079, China.
Int J Genomics. 2017;2017:2175871. doi: 10.1155/2017/2175871. Epub 2017 Aug 15.
Wenxin Granule (WXKL) is a traditional Chinese medicine used for treatment of myocardial infarction (MI) and arrhythmias. However, the genomic pathological mechanisms of MI and mechanisms of WXKL are largely unknown. This study aims to investigate a comprehensive miRNA expression profile, and the predicted correlation pathways to be targeted by differentially expressed miRNAs in MI, and mechanisms of WXKL from a gene level. MI rat model was established by a coronary artery ligation surgery. miRNA expression microarrays were performed and the data were deposited in Gene Expression Omnibus (GEO number GSE95855). And, pathway analysis was performed by using the DIANA-miRPath v3.0 online tool. The expressions of miR-1, miR-133, Cx43, and Cx45 were detected by quantitative real-time PCR. It was found that 35 differentially expressed miRNAs and 23 predicted pathways, including miR-1, miR-133, and gap junction pathway, are involved in the pathogenesis of MI. And, WXKL increased the expressions of miR-1 and miR-133, while also increased the mRNA levels of Cx43 and Cx45, and, especially, recovered the Cx43/Cx45 ratio near to normal level. The results suggest that regulatory effects on miR-1, miR-133, Cx43, and Cx45 might be a possible mechanism of WXKL in the treatment of MI at the gene level.
稳心颗粒（WXKL）是一种用于治疗心肌梗死（MI）和心律失常的中药。然而，MI的基因组病理机制以及WXKL的作用机制在很大程度上尚不清楚。本研究旨在从基因水平研究MI中全面的miRNA表达谱、差异表达miRNA预测的相关靶向通路以及WXKL的作用机制。通过冠状动脉结扎手术建立MI大鼠模型。进行miRNA表达微阵列检测，并将数据存入基因表达综合数据库（GEO编号GSE95855）。并且，使用DIANA-miRPath v3.0在线工具进行通路分析。通过定量实时PCR检测miR-1、miR-133、Cx43和Cx45的表达。研究发现，35个差异表达的miRNA和23条预测通路，包括miR-1、miR-133和缝隙连接通路，参与了MI的发病机制。并且，WXKL增加了miR-1和miR-133的表达，同时也增加了Cx43和Cx45的mRNA水平，特别是使Cx43/Cx45比值恢复到接近正常水平。结果表明，对miR-1、miR-133、Cx43和Cx45的调控作用可能是WXKL在基因水平治疗MI的一种可能机制。
