The Preventive Effect of Cardiac Sympathetic Denervation Induced by 6‐OHDA on Myocardial Ischemia–Reperfusion Injury: The Changes of lncRNA/circRNAs‐miRNA‐mRNA Network of the Upper Thoracic Spinal Cord in Rats

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.

Deregulated RNAs involved in sympathetic regulation of sepsis-induced acute lung injury based on whole transcriptome sequencing

“…Sympathetic nerves participate in several pathophysiological processes by affecting the expression of ncRNAs. NE downregulated miR-19a-3p in vitro [ 10 ], while SD can improve cardiac ischemia–reperfusion in rats and affect the expression of mRNAs, miRNAs, lncRNAs, and circRNAs in the thoracic sympathetic trunk [ 50 ]. Sympathetic nerves can transmit miRNA-181a, which is involved in the regulation of hypertension [ 11 ], and postmyocardial infarction cardiac insufficiency can be improved by miRNA [ 51 ].…”

Atorvastatin Inhibits Ferroptosis of H9C2 Cells by regulatingSMAD7/Hepcidin Expression to Improve Ischemia-Reperfusion Injury

“…A total of 18 Wistar rats (250∼300 g) were purchased from Hunan slake Jingda experimental animal Co., Ltd. Te rats were randomly divided into the Sham group, I/R group, and I/R + ATV group (n � 6/group).Tey received standard diet and water before myocardial I/R. Rats in the I/R + ATV group were orally treated with ATV (10 mg/kg/d) for 2 weeks before myocardial I/R (9).Te Sham and I/R model rats [9,20] were constructed as follows: Te rats were anesthetized with sodium pentobarbital (50 mg/kg, intraperitoneal injection), ligation of the left anterior descending branch with 4-0 silk thread for 30 min, and then reperfusion for 180 min. In the sham control group, the entire procedure was performed with silk thread passing below the coronary artery, but the LAD coronary artery was not ligated.…”

miR-6315 silencing protects against spinal cord injury through the Smo and anti-ferroptosis pathway

“…Mature miRNAs negatively affect the post-transcriptional regulation of genes by forming complementary pairs with target mRNAs, resulting in mRNA translational repression or degradation [ 23 ]. Although the relationship between the miRNAs and mRNAs is well-investigated, the regulatory relationship between miRNAs and target mRNAs in the spinal cord post-SCI remains unclear [ 24 ]. Therefore, a comprehensive analysis of miRNAs and mRNAs to analyze the miRNA–mRNA axis within SCI must be performed.…”