桃红四物汤对大脑中动脉闭塞大鼠环状RNA表达谱的影响  

Effects of Tao Hong Si Wu decoction on circular RNA expression profiles in rats with middle cerebral artery occlusion

作　　者：费长义 张丽娟 王倪 褚福瑞 余超 薛苏君 潘凌宇[1] 彭代银 段贤春[1,2,3] FEI Chang-yi;ZHANG Li-juan;WANG Ni;CHU Fu-rui;YU Chao;XUE Su-jun;PAN Ling-yu;PENG Dai-yin;DUAN Xian-chun(Dept of Pharmacy,the First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China;School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;Key Laboratory of Chinese Medicinal Formula Research,Anhui University of Chinese Medicine,Hefei 230012,China)

机构地区：[1]安徽中医药大学第一附属医院药学部,安徽合肥230031 [2]安徽中医药大学药学院,安徽合肥230012 [3]安徽中医药大学中药复方安徽省重点实验室,安徽合肥230012

出　　处：《中国药理学通报》2024年第5期954-963,共10页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 82074059);新安医学教育部重点实验室开放基金项目(No 2022XAYX07);安徽省2023年度高等学校科研计划项目(No 2023AH050745)。

摘　　要：目的筛选和研究桃红四物汤(Taohong Siwu Decoction,THSWD)对大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)大鼠环状RNA(circular RNA,circRNA)表达的影响,探讨THSWD的可能作用及分子机制。方法采用下一代RNA测序技术检测THSWD治疗后MCAO大鼠circRNA表达谱,并与MCAO模型组和对照组进行比较。生物信息学分析预测潜在的靶向微小RNA(micro RNA,miRNA)和mRNAs。应用GO富集分析和KEGG通路富集分析方法分析差异表达的circRNAs的潜在作用。对表达差异显著的circRNA进行RT-qPCR验证。结果MCAO组与对照组之间存在87个差异表达的circRNA,MCAO组与THSWD组之间存在86个差异表达的circRNA。其中,THSWD可逆转MCAO模型诱导的17个circRNAs。为了证明DECs靶向的mRNAs的作用,使用了GO和KEGG数据库。进一步分析表明,5个表达差异显著circRNAs表达量与测序结果相似。结论首次确定了THSWD治疗后MCAO大鼠circRNAs的全面表达谱,提示THSWD对MCAO的治疗作用可能是通过调节circRNAs的表达实现的。Aim To screen and study the effects of Tao Hong Si Wu decoction(THSWD)-mediated treatment on circular RNA(circRNA)expression profiles in rats with middle cerebral artery occlusion(MCAO),and investigate the possible roles and molecular mechanisms of THSWD.Methods Next-generation RNA sequencing was conducted to identify circRNA expression profiles in MCAO rats after treatment with THSWD and compared with the MCAO model group and control group.Bioinformatics analysis was performed to predict the potential target microRNAs and mRNAs.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses for the potential target mRNAs were applied to explore the potential roles of differentially expressed circRNAs.RT-qPCR was performed to verify circRNAs with significant differences in expression.Results We identified 87 significantly differentially expressed circRNAs between the MCAO group versus the control group,and 86 significantly differentially expressed circRNAs between the MCAO group versus the THSWD group.respectively.Among them,17 circRNAs induced by the MCAO model were reversed via treatment with THSWD.To demonstrate the roles of mRNAs targeted by DECs,the GO and KEGG databases were used.Further analysis revealed that five circRNAs may play important roles in the development of MCAO.Conclusions The comprehensive expression profile of circRNAs in rats with middle cerebral artery occlusion after THSWD treatment is determined for the first time,suggesting that the therapeutic effect of THSWD on MCAO may be achieved by regulating the expression of circRNAs.

关 键 词：桃红四物汤 大脑中动脉闭塞 环状RNA 生物信息学 下一代RNA测序 缺血性卒中 

分 类 号：R-332[医药卫生] R289.5R322.12R342.2R743.31