研究动态
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Corylin 促进 Raf-1/ASK1 复合物形成,抑制心肌缺血/再灌注损伤中的细胞凋亡。

Promotion of Raf-1/ASK1 complex formation by corylin inhibits cell apoptosis in myocardial ischemia/reperfusion injury.

发表日期:2024 Aug 11
作者: Kaiyu Huang, Chenchen Cai, Hualing He, Binghua Yi, Wencai Xu, Zhonghao Lin, Xiao Lv, Ronghua Liu, Cheng Zheng, Yingying Zhou, Jiafeng Lin
来源: INTERNATIONAL IMMUNOPHARMACOLOGY

摘要:

心肌缺血再灌注(MIR)损伤的有效治疗仍然是一个未得到满足的临床需求。心肌细胞凋亡在此阶段很常见,并构成重大风险。 Corylin 是从 Psoralea corylifolia L. 中提取的一种黄酮类化合物,已被证明具有抗炎、抗癌和抗动脉粥样硬化特性。然而,Corylin 是否以及如何影响 MIR 损伤仍不清楚。在这项研究中,我们利用体内和体外左前降支(LAD)冠状动脉结扎和氧糖剥夺和再灌注(OGD/R)模型,探讨了Corylin作为MI/R损伤的有效治疗剂的机制。 。采用TUNEL、Annexin-V/PI双染、Ki67免疫组化、蛋白质印迹分析和免疫荧光来验证细胞凋亡水平和Raf-1/ASK1复合物活性。使用分子对接、corylin-Raf-1 结合测定和免疫共沉淀 (Co-IP) 检测 corylin 和 Raf-1/ASK1 复合物之间的相互作用。此外,还进行了TTC染色、超声心动图、HE染色、Masson三色染色和血清学测试来评估corylin的体内心脏保护作用。这些研究结果表明,corylin 可减少 MIR 损伤诱导的心肌细胞凋亡并改善心脏功能。从机制上讲,Corylin可以与Raf-1相互作用,促进Raf-1/ASK1复合物的形成,从而抑制心肌细胞凋亡。总之,我们的结果表明,Corylin 通过减少心肌细胞凋亡来改善 MIR 损伤后的心脏功能障碍。版权所有 © 2024 Elsevier B.V. 保留所有权利。
Effective treatment of myocardial ischemia-reperfusion (MIR) injury remains an unmet clinical need. Cardiomyocyte apoptosis is common at this stage and poses a significant risk. Corylin, a flavonoid compound extracted from Psoralea corylifolia L., has been shown to have anti-inflammatory, anticancer, and antiatherosclerotic properties. However, whether and how corylin affects MIR injury remain unclear. In this study, we explored the mechanism of corylin as a potent therapeutic agent for MI/R injury, using a left anterior descending (LAD) coronary artery ligation and oxygen-glucose deprivation and reperfusion (OGD/R) model in vivo and in vitro. TUNEL, Annexin-V/PI double staining,Ki67 immunohistochemistry, western blot analysis, and immunofluorescence were used to validate cell apoptosis level and Raf-1/ASK1 complex activity. The interaction between corylin and Raf-1/ASK1 complex was detected using molecular docking, corylin-Raf-1 binding assays, and coimmunoprecipitation (Co-IP). Moreover, TTC staining, echocardiography, HE staining, Masson trichrome staining and serological testing were performed to assess the cardioprotective effects of corylin in vivo. These findings showed that corylin reduces MIR injury-induced cardiomyocyte apoptosis and improves cardiac function. Mechanistically, corylin can interact with Raf-1 and promote the formation of the Raf-1/ASK1 complex, thus inhibiting cardiomyocyte apoptosis. In conclusion, our results demonstrate that corylin ameliorated cardiac dysfunction after MIR injury by reducing myocardial apoptosis.Copyright © 2024 Elsevier B.V. All rights reserved.