Analyses of changes in myocardial long non-coding RNA and mRNA profiles after severe hemorrhagic shock and resuscitation via RNA sequencing in a rat model

作者：Lin, Lin; Yang, Zhengfei; Zheng, Guanghui; Zhuansun, Yongxun; Wang, Yue; Li, Jianguo; Chen, Rui^*; Tang, Wanchun^*

来源：BMC Molecular Biology, 2018, 19(1): 11.

DOI：10.1186/s12867-018-0113-8

• Hemorrhagic shock
• Ischemia reperfusion injury
• Long non-coding RNA
• STAT3
• High-throughput RNA sequencing

BackgroundIschemia-reperfusion injury has been proven to induce organ dysfunction and death, although the mechanism is not fully understood. Long non-coding RNAs (lncRNAs) have drawn wide attention with their important roles in the gene expression of some biological processes and diseases, including myocardial ischemia-reperfusion (I/R) injury. In this paper, a total of 26 Sprague-Dawley (SD) rats were randomized into two groups: sham and ischemia-reperfusion (I/R) injury. Hemorrhagic shock was induced by removing 45% of the estimated total blood volume followed by reinfusion of shed blood. High-throughput RNA sequencing was used to analyze differentially expressed (DE) lncRNAs and messenger RNAs (mRNAs) in the heart tissue 4h after reperfusion. Myocardial function was also evaluated.ResultsAfter resuscitation, the decline of myocardial function of shocked animals, expressed by cardiac output, ejection fraction, and myocardial performance index (MPI), was significant (p<0.05). DE lncRNAs and mRNAs were identified by absolute value of fold change2 and the false discovery rate 0.001. In rats from the I/R injury group, 851 lncRNAs and 1015 mRNAs were significantly up-regulated while 1533 lncRNAs and 1702m RNAs were significantly down-regulated when compared to the sham group. Among the DE lncRNAs, we found 12 location-associated with some known apoptosis-related protein-coding genes which were up-regulated or down-regulated accordingly, including STAT3 and Il1r1. Real time PCR assays confirmed that the expression levels of five location-associated lncRNAs (NONRATT006032.2, NONRATT006033.2, NONRATT006034.2, NONRATT006035.2 and NONRATT029969.2) and their location-associated mRNAs (STAT3 and Il1r1) in the rats from the I/R injury group were all significantly up-regulated versus the sham group.ConclusionsThe DE lncRNAs (NONRATT006032.2, NONRATT006033.2, NONRATT006034.2 and NONRATT006035.2) could be compatible with their role in myocardial protection by stimulating their co-located gene (STAT3) after hemorrhagic shock and resuscitation. The final prognosis of I/R injury might be regulated by different genes, which is regarded as a complex network.

• 出版日期2018-11-1
• 单位中山大学