Jiang Wenbing, Jiang Lelin, Liu Yiying, Zhao Xiaoli, Huang Shu'e, Liu Ying, Sun Huanghui, Guan Fanlu
Department of Cardiology, Wenzhou Integrated Traditional Chinese and Western Medicine Hospital, 325000, Wenzhou, Zhejiang, China.
The Second Clinical College of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China.
Herz. 2025 Sep 10. doi: 10.1007/s00059-025-05334-w.
The protective function of the tetrandrine (TET)-mediated transient receptor potential vanilloid 2 (TRPV2) channel in myocardial ischemia/reperfusion injury (MI/RI) has been established in numerous investigations. The objective of the current study was to explain how TRPV2 further modulates downstream factors to influence the progression of MI/RI.
To this end, an MI/RI model in rats and a hypoxia-reoxygenation (H/R) cell model in H9c2 cells were constructed. Based on western blotting analyses, the effects of TRPV2 on the levels of apoptosis-related proteins as well as calcineurin and nuclear factor of activated T cells (NFAT) were ascertained. Evans blue/triphenyltetrazolium chloride (TTC) double staining and H&E staining were, respectively, used to examine the pathological changes and infarction size of myocardial tissues in rats. Cardiomyocyte apoptosis was assessed with TUNEL assays and flow cytometry. Ca concentration and reactive oxygen species (ROS) production were determined using a calcium assay kit and dichlorodihydrofluorescein diacetate (DCFH-DA) staining, respectively.
Downregulated TRPV2 showed a significant ameliorative effect on cardiomyocyte histopathology and infarction area. Cardiomyocyte apoptosis, Ca concentration, and ROS amounts were also inhibited when TRPV2 was silenced. Furthermore, results indicated that TET could significantly decrease TRPV2, while knocking down TRPV2 markedly suppressed the expression of calcineurin and NFAT.
These findings shed light on the possible mechanisms behind the TET-mediated TRPV2 channel in MI/RI, indicating that TET has protective functions through downregulation of TRPV2 expression and suppression of the Ca/calcineurin/NFAT pathway.
粉防己碱（TET）介导的瞬时受体电位香草酸亚型2（TRPV2）通道在心肌缺血/再灌注损伤（MI/RI）中的保护作用已在众多研究中得到证实。本研究的目的是解释TRPV2如何进一步调节下游因子以影响MI/RI的进展。
为此，构建了大鼠MI/RI模型和H9c2细胞缺氧/复氧（H/R）细胞模型。基于蛋白质免疫印迹分析，确定TRPV2对凋亡相关蛋白以及钙调神经磷酸酶和活化T细胞核因子（NFAT）水平的影响。分别采用伊文思蓝/氯化三苯基四氮唑（TTC）双重染色和苏木精-伊红（H&E）染色来检测大鼠心肌组织的病理变化和梗死面积。通过TUNEL检测和流式细胞术评估心肌细胞凋亡。分别使用钙检测试剂盒和二氯二氢荧光素二乙酸酯（DCFH-DA）染色来测定钙浓度和活性氧（ROS）的产生。
下调的TRPV2对心肌细胞组织病理学和梗死面积有显著改善作用。沉默TRPV2时，心肌细胞凋亡、钙浓度和ROS量也受到抑制。此外，结果表明TET可显著降低TRPV2，而敲低TRPV2可明显抑制钙调神经磷酸酶和NFAT的表达。
这些发现揭示了TET介导的TRPV2通道在MI/RI中的可能机制，表明TET通过下调TRPV2表达和抑制Ca/钙调神经磷酸酶/NFAT途径发挥保护作用。
