关键词: Fibrosis and apoptosis Myocardial Infarction Wnt/β-catenin signalling pathway XAV939

Mesh : Male Mice Animals Myocardium / metabolism beta Catenin / metabolism Mice, Inbred C57BL Myocardial Infarction / drug therapy Wnt Signaling Pathway Prognosis Fibrosis Apoptosis Disease Models, Animal Heterocyclic Compounds, 3-Ring

来  源:   DOI:10.1007/s12010-023-04485-y

Abstract:
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.
摘要:
心肌梗死(MI)与Wnt信号通路密切相关,但是XAV939(一种Wnt/β-catenin信号通路阻断剂)在MI中的作用尚未阐明。目的探讨XAV939在小鼠心脏中的作用,为改善MI预后提供一种新的可行的治疗方法。C57BL/6(男性,8周大,选择20-25g)小鼠进行我们的研究。结扎左冠状动脉前降支制作MI模型。手术后第28天,心脏功能通过超声心动图检查。梗死面积,纤维化,血管生成通过TTC分析单独测量,马森三色染色,和CD31分析,分别。通过TdT介导的dUTP缺口末端标记(TUNEL)染色检查细胞凋亡。Wnt的表达,β-连环蛋白,caspase3,Bax,通过蛋白质印迹法测定Bcl-2。XAV939通过促进β-catenin的降解成功阻断MI后心肌细胞中Wnt/β-catenin信号通路的激活。XAV939抑制纤维化和凋亡,促进血管生成,心肌梗死后心肌梗死面积减少,心功能改善。XAV939可以通过阻断Wnt/β-catenin信号通路来减少心肌梗死面积和改善心功能,可能为改善MI预后提供新的策略。
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