Abstract
In this study, we investigated whether chemical 6-hydroxydopamine (6-OHDA) stimuli caused cardiac sympathetic denervation (SD), and we analyzed gene expression profiles to determine the changes in the lncRNA/circRNAs-miRNA-mRNA network in the affected spinal cord segments to identify putative target genes and molecular pathways in rats with myocardial ischemia–reperfusion injury (MIRI). Our results showed that cardiac sympathetic denervation induced by 6-OHDA alleviated MIRI. Compared with the ischemia reperfusion (IR, MIRI model) group, there were 148 upregulated and 51 downregulated mRNAs, 165 upregulated and 168 downregulated lncRNAs, 70 upregulated and 52 downregulated circRNAs, and 12 upregulated and 11 downregulated miRNAs in the upper thoracic spinal cord of the SD-IR group. Furthermore, we found that the differential genes related to cellular components were mainly enriched in extracellular and cortical cytoskeleton, and molecular functions were mainly enriched in chemokine activity. Pathway analysis showed that the differentially expressed genes were mainly related to the interaction of cytokines and cytokine receptors, sodium ion reabsorption, cysteine and methionine metabolism, mucoglycan biosynthesis, cGMP-PKG signaling pathway, and MAPK signaling pathway. In conclusion, the lncRNA/circRNAs-miRNA-mRNA networks in the upper thoracic spinal cord play an important role in the preventive effect of cardiac sympathetic denervation induced by 6-OHDA on MIRI, which offers new insights into the pathogenesis of MIRI and provides new targets for MIRI.
Highlights
Myocardial ischemia/reperfusion injury (MIRI) accounts for a large proportion of the total incidence of heart diseases, and it seriously affects human quality of life [1,2,3]
We examined the preventive effect of cardiac sympathetic denervation induced by 6-OHDA, a catecholamine-specific toxin [12], on MIRI rats
We observed the development of ST-segment elevation and QRS complex changes on an electrocardiogram; there was a cyanotic change in the myocardium of the occluded area 30 minutes after cardiac ischemia
Summary
Myocardial ischemia/reperfusion injury (MIRI) accounts for a large proportion of the total incidence of heart diseases, and it seriously affects human quality of life [1,2,3]. Previous studies have reported the cellular and molecular mechanisms of neural–cardiac interactions [4, 5] during pathological remodeling after MIRI [6]. To date, no effective methods have been found to prevent MIRI. Cardiac nerves, comprising both the sensory nerves and the autonomic nerves, transmit the information from the heart to the spinal cord and brain, which results in an appropriate sympathetic neural outflow [7]. Experimental studies have shown that cardiac innervation abnormality is an important cause of the sympathetic nervous system overactivity. Several studies have reported the vital role of the sympathetic nerves in MIRI progression, and sympathetic nerves have been shown
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