抗纤益心方通过MCU通路改善扩张型心肌病小鼠心肌纤维化的研究OA

Objective To investigate the effect of Kangxian Yixin Formula(抗纤益心方,KXYXF)on myocardial fibrosis(MF)in mice with dilated cardiomyopathy(DCM)and its relationship with the mitochondrial calcium uniporter(MCU)-mediated calcium signal-ing pathway.Methods Forty DCM model mice were randomly divided into four groups(n=10 per group):model,KXYXF,captopril,and KXYXF+captopril combination.An additional 10 healthy mice served as the normal control group.After 8 weeks of treatment,car-diac function was evaluated by echocardiography,measuring left ventricular end-diastolic diameter(LVEDd),left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS).Myocardial pathology and collagen deposition were assessed by hematoxylin-eosin(HE)and Masson staining.Mitochondrial ultrastructure was examined by transmission electron microscopy(TEM).The expression of MCU,calmodulin(CaM),nuclear factor of activated T cells 4(NFAT4),collagen type I(COL-1),and alpha-smooth muscle actin(α-SMA)was detected at the mRNA and protein levels by polymerase chain reaction(PCR)and Western blot(WB),respectively.Results Compared with the normal control group,the model group exhibited impaired cardiac function(increased LVEDd,decreased LVEF and LVFS),disorganized myocardial architecture,significant fibrosis,mitochondrial damage,and upregu-lated expression of MCU,CaM,NFAT4,COL-1,and α-SMA(P<0.05 or P<0.01).Treatment with KXYXF significantly improved cardiac function,attenuated MF and mitochondrial injury,and downregulated the expression of MCU,CaM,NFAT4,α-SMA,and COL-1 compared with the model group(P<0.05 or P<0.01).Conclusion KXYXF alleviates MF and improves cardiac function in DCM mice,potentially through modulation of the MCU-mediated calcium transport pathway.