Integrated Bioinformatics Analysis and Verification of Gene Targets for Myocardial Ischemia-Reperfusion Injury

心肌缺血再灌注损伤基因靶点的综合生物信息学分析与验证

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作者:Jianru Wang, Xiaohui Li, Guangcao Peng, Genhao Fan, Mengmeng Zhang, Jian Chen

Background

Myocardial ischemia-reperfusion injury (MIRI) has become a thorny and unsolved clinical problem. The pathological mechanisms of MIRI are intricate and unclear, so it is of great significance to explore potential hub genes and search for some natural products that exhibit potential therapeutic efficacy on MIRI via targeting the hub genes.

Conclusions

Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be critical in the pathological process of MIRI, and the natural products (araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) targeting these hub genes exhibited potential therapeutic efficacy on MIRI. Our findings provided new insights to explore the mechanism and treatments for MIRI and revealed new therapeutic targets for natural products with protective properties against MIRI.

Methods

First, the differential expression genes (DEGs) from GSE58486, GSE108940, and GSE115568 were screened and integrated via a robust rank aggregation algorithm. Then, the hub genes were identified and verified by the functional experiment of the MIRI mice. Finally, natural products with protective effects against MIRI were retrieved, and molecular docking simulations between hub genes and natural products were performed.

Results

230 integrated DEGs and 9 hub genes were identified. After verification, Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be the most significant genes during MIRI. A total of 75 natural products were discovered. Most of them (especially araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) showed good ability to bind the hub genes. Conclusions: Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be critical in the pathological process of MIRI, and the natural products (araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) targeting these hub genes exhibited potential therapeutic efficacy on MIRI. Our findings provided new insights to explore the mechanism and treatments for MIRI and revealed new therapeutic targets for natural products with protective properties against MIRI.

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