Wang Jianru, Li Xiaohui, Peng Guangcao, Fan Genhao, Zhang Mengmeng, Chen Jian
Department of Cardiovascular, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan 450099, China.
Department of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China.
Evid Based Complement Alternat Med. 2022 Apr 15;2022:2056630. doi: 10.1155/2022/2056630. eCollection 2022.
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.
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.
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.
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.
心肌缺血再灌注损伤（MIRI）已成为一个棘手且尚未解决的临床问题。MIRI的病理机制复杂且尚不清楚，因此探索潜在的枢纽基因并寻找一些通过靶向枢纽基因对MIRI具有潜在治疗效果的天然产物具有重要意义。
首先，通过稳健秩聚合算法筛选并整合来自GSE58486、GSE108940和GSE115568的差异表达基因（DEG）。然后，通过MIRI小鼠的功能实验鉴定并验证枢纽基因。最后，检索对MIRI具有保护作用的天然产物，并进行枢纽基因与天然产物之间的分子对接模拟。
鉴定出230个整合的DEG和9个枢纽基因。经验证，Emr1、Tyrobp、Itgb2、Fcgr2b、Cybb和Fcer1g可能是MIRI过程中最关键的基因。共发现75种天然产物。其中大多数（尤其是紫茎泽兰苷C、甘草酸、麦冬皂苷D、重楼皂苷I和石榴皮素）显示出与枢纽基因良好的结合能力。
Emr1、Tyrobp、Itgb2、Fcgr2b、Cybb和Fcer1g可能在MIRI的病理过程中起关键作用，靶向这些枢纽基因的天然产物（紫茎泽兰苷C、甘草酸、麦冬皂苷D、重楼皂苷I和石榴皮素）对MIRI具有潜在治疗效果。我们的研究结果为探索MIRI的机制和治疗方法提供了新的见解，并揭示了具有抗MIRI保护特性的天然产物的新治疗靶点。
