The Effect on LRP6 via Regulating Canonical Wnt/β-catenin Signaling in Doxorubicin-induced Cardiomyocyte Injury / 中山大学学报(医学科学版)

ABSTRACT

@#【Objective】To investigate the function of LRP6 and canonical Wnt/β-catenin signaling pathway in Doxorubicin-induced cardiomyopathy.【Methods】To establish the model of Dox cardiomyopathy in vitro and in vivo，H9C2 cells were treated with Dox（1 μmol/L）for 12 h and twelve SD rats were divided into two groups equally，and intraperitoneally injected with normal saline and Dox respectively. The changes of protein and mRNA levels were detected by western blot and qPCR. Cardiomyocytes were transfected with siRNA to knockdown LRP6. Mitochondrial membrane potential，nuclear condensation and matrix swelling were determined by Rhodamine 123 ，Hoechst and Mitotracker staining respectively. The apoptosis rate of cells was measured by flow cytometric analysis. 【Results】 The model of Dox cardiomyopathy was successfully established in vitro and in vivo. Dox downregulated the mRNA and protein levels of LRP6. Knockdown of LRP6 aggravated the cell apoptosis and mitochondrial damage induced by Dox. Both Dox and silencing LRP6 induced the downregulation of β - catenin ，and activation of β - catenin reversed the cardiomyocytes apoptosis caused by Dox. 【Conclusions】 Dox downregulated the expression of LRP6 and inhibited canonical Wnt/β- catenin signaling pathway，thus causing cardiomyocytes apoptosis and mitochondrial dysfunction.