山奈酚通过PHB2-PKM2介导的线粒体和内质网稳态改善脓毒性冠状动脉微血管损伤
Kaempferol ameliorates septic coronary microvascular injury through PHB2-PKM2 mediated mitochondria and endoplasmic reticulum homeostasis.
摘要(中文译文)
线粒体功能障碍和内质网应激是冠状动脉微血管损伤的关键促成因素。中医药在治疗冠状动脉微血管损伤方面显示出显著优势。然而，KA发挥其作用的确切机制，特别是通过抑制素2（PHB2）和丙酮酸激酶M2（PKM2）通路治疗脓毒症冠状动脉微血管损伤的机制，仍未被充分了解。本研究旨在探讨KA通过PHB2/PKM2通路调节线粒体和内质网稳态，从而改善脓毒症冠状动脉微血管损伤的机制。本研究利用PHB2特异性敲除（PHB2）和转基因（PHB2）小鼠模型，以及PHB2敲低（siRNA-PHB2）、PHB2过表达（ad-PHB2）、PKM2敲低（siRNA-PKM2）和PKM2过表达（ad-PKM2）的冠状动脉微血管内皮细胞模型，探讨山柰酚在脓毒症冠状动脉微血管损伤中的作用。KA处理通过PHB2/PKM2通路增强线粒体稳定性、调节线粒体质量控制（MQC）系统、抑制钙超载，并减轻心脏炎症和心肌微血管功能障碍。分子对接证实了PHB2与PKM2之间的直接相互作用以及KA的作用靶点。KA通过PHB2/PKM2信号通路调节MQC、抑制内质网应激损伤并平衡线粒体与内质网稳态，从而对脓毒症冠状动脉微血管损伤发挥保护作用。
Abstract
Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are pivotal contributors to coronary microvascular injury. Traditional Chinese medicine (TCM) has shown remarkable advantages in treating coronary microvascular injury. Nevertheless, the exact mechanisms by which KA exerts its effects, especially through the Prohibitin 2 (PHB2) and pyruvate kinase M2 (PKM2) pathway for treating coronary microvascular injury in sepsis, are still not well understood. This study aims to investigate the mechanism by which KA modulates mitochondrial and ER homeostasis through the PHB2/PKM2 pathway, thereby ameliorating septic coronary microvascular injury. PHB2-specific knockout (PHB2) and transgenic (PHB2) mouse models, along with coronary microvascular endothelial cell models with PHB2 knockdown (siRNA-PHB2), PHB2 overexpression (ad-PHB2), PKM2 knockdown (siRNA-PKM2), and PKM2 overexpression (ad-PKM2), were utilized to explore the roles of Kaempferol in septic coronary microvascular injury. KA treatment enhanced mitochondrial stability, modulated the mitochondrial quality control (MQC) system, inhibited calcium overload, and attenuated cardiac inflammation and myocardial microvascular dysfunction through the PHB2/PKM2 pathway. Molecular docking confirmed the direct interaction between PHB2 and PKM2 and the target of KA action. KA plays a protective role against septic coronary microvascular injury by regulating MQC, inhibiting ER stress injury, and balancing mitochondria and ER homeostasis through the PHB2/PKM2 signaling pathway.
如何引用
AMA
Xiangyi Pu, Xinai Zhang, Zhaoqi Yan, Xuanke Guan, Jinfeng Liu, Yanli Wang, et al. Kaempferol ameliorates septic coronary microvascular injury through PHB2-PKM2 mediated mitochondria and endoplasmic reticulum homeostasis.. European journal of pharmacology. 2026; doi:10.1016/j.ejphar.2026.178773.
APA
Xiangyi Pu, Xinai Zhang, Zhaoqi Yan, Xuanke Guan, Jinfeng Liu, Yanli Wang, et al (2026). Kaempferol ameliorates septic coronary microvascular injury through PHB2-PKM2 mediated mitochondria and endoplasmic reticulum homeostasis.. European journal of pharmacology. https://doi.org/10.1016/j.ejphar.2026.178773
GB/T 7714
Xiangyi Pu, Xinai Zhang, Zhaoqi Yan, Xuanke Guan, Jinfeng Liu, Yanli Wang, et al. Kaempferol ameliorates septic coronary microvascular injury through PHB2-PKM2 mediated mitochondria and endoplasmic reticulum homeostasis.[J]. European journal of pharmacology, 2026 doi:10.1016/j.ejphar.2026.178773.
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