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Updated: Jul 20, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
RNA-seq based transcriptomic map reveals multiple pathways of necroptosis in treating myocardial ischemia reperfusion
Yijia Zhang1, Qingbiao Song1, Sihan E1
1School of Anesthesiology, Weifang Medical University, Weifang 261053, China.
Abstract:
Necroptosis has been shown to contribute to myocardial ischemia reperfusion injury (MIRI). This study aims to gain new insights into the signaling pathway of necroptosis in rat MIRI using RNA sequencing. MIRI was induced in male rats by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 120 min. RNA sequencing was performed to obtain mRNA profiles of MIRI group and MIRI group treated with necrostatin-1 (Nec-1,an inhibitor of necroptosis). Differentially expressed genes (DEGs) were then identified. The DEGs were prominently enriched in the TNF-α signaling pathway, the MAPK signaling pathway and cytokine-cytokine receptor pathways. The majority of the results were associated with genes like Thumpd3,Egr2,Dot1l,Cyp1a1,Dbnl,which primarily regulate inflammatory response and apoptosis, particularly in myocardium. The above results suggested that Nec-1 might be involved in the regulation of necroptosis and the inflammatory response through the above-mentioned genes.
Insights
Necroptosis contributes to myocardial ischemia reperfusion injury (MIRI). This study used RNA sequencing to identify key genes and pathways, revealing necrostatin-1 (Nec-1) may regulate necroptosis and inflammation in MIRI.
Area of Science:
- Cardiovascular Biology
- Molecular Pathology
- Genomics
Background:
- Necroptosis, a programmed form of necrosis, plays a significant role in myocardial ischemia reperfusion injury (MIRI).
- Understanding the molecular mechanisms and signaling pathways involved in MIRI is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the signaling pathways of necroptosis in a rat model of MIRI using RNA sequencing.
- To identify differentially expressed genes (DEGs) and their associated pathways regulated by necrostatin-1 (Nec-1), an inhibitor of necroptosis.
Main Methods:
- Myocardial ischemia reperfusion injury (MIRI) was induced in male rats.
- RNA sequencing was performed on myocardial tissue from MIRI and Nec-1 treated MIRI groups.
- Differentially expressed genes (DEGs) were identified and subjected to pathway enrichment analysis.
Main Results:
- DEGs were significantly enriched in TNF-α signaling, MAPK signaling, and cytokine-cytokine receptor pathways.
- Key genes identified include Thumpd3, Egr2, Dot1l, Cyp1a1, and Dbnl, which are involved in inflammatory response and apoptosis.
- Necrostatin-1 (Nec-1) treatment modulated the expression of these genes.
Conclusions:
- Necroptosis is implicated in MIRI, involving specific signaling pathways and gene expression profiles.
- Necrostatin-1 (Nec-1) may exert its protective effects by regulating necroptosis and inflammatory responses via modulation of identified genes.
- These findings provide insights into the molecular mechanisms of MIRI and potential therapeutic targets.
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