Zhang Zhu, Qi Jiancheng, Fan Xiucai, Pan Min
Department of Cardiology, Jianhu Clinical College, Jiangsu Vocational College of Medicine, 224700, Yancheng, China.
Department of Cardiology, West China (Sanya) Hospital, Sichuan University, No. 228 Jiefang Road, Sanya, 572022, Hainan, China.
Appl Biochem Biotechnol. 2024 Feb;196(2):605-615. doi: 10.1007/s12010-023-04485-y. Epub 2023 May 11.
Myocardial infarction (MI) is closely related to the Wnt signalling pathway, but the role of XAV939 (a Wnt/β-catenin signalling pathway blocker) in MI has not been elucidated. The purpose of this study was to explore the role of XAV939 in mouse hearts and to provide a new and feasible treatment for improving the prognosis of MI. C57BL/6 (male, 8 weeks old, 20-25 g) mice were selected for our study. The MI model was made by ligating the left anterior descending coronary artery. On day 28 after the operation, cardiac function was examined by echocardiography. Infarct size, fibrosis, and angiogenesis were individually measured by TTC assays, Masson's trichrome staining, and CD31 analysis, respectively. Apoptosis was examined by TdT-mediated dUTP nick-end labelling (TUNEL) staining. The expression of Wnt, β-catenin, caspase 3, Bax, and Bcl-2 was determined by western blotting. XAV939 successfully blocked Wnt/β-catenin signalling pathway activation in cardiomyocytes after MI by promoting the degradation of β-catenin. XAV939 suppressed fibrosis and apoptosis, promoted angiogenesis, reduced myocardial infarct size and improved cardiac function after MI. XAV939 can reduce myocardial infarct size and improve cardiac function by blocking the Wnt/β-catenin signalling pathway, which may provide a new strategy for improving the prognosis of MI.
心肌梗死(MI)与Wnt信号通路密切相关,但XAV939(一种Wnt/β-连环蛋白信号通路阻滞剂)在MI中的作用尚未阐明。本研究的目的是探讨XAV939在小鼠心脏中的作用,并为改善MI的预后提供一种新的可行治疗方法。我们的研究选用了C57BL/6(雄性,8周龄,20 - 25克)小鼠。通过结扎左冠状动脉前降支制作MI模型。术后第28天,通过超声心动图检查心脏功能。梗死面积、纤维化和血管生成分别通过TTC测定、Masson三色染色和CD31分析进行测量。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)染色检测细胞凋亡。通过蛋白质印迹法测定Wnt、β-连环蛋白、半胱天冬酶3、Bax和Bcl-2的表达。XAV939通过促进β-连环蛋白的降解成功阻断了MI后心肌细胞中Wnt/β-连环蛋白信号通路的激活。XAV939抑制了纤维化和细胞凋亡,促进了血管生成,减小了MI后的心肌梗死面积并改善了心脏功能。XAV939可通过阻断Wnt/β-连环蛋白信号通路减小心肌梗死面积并改善心脏功能,这可能为改善MI的预后提供一种新策略。