Action mechanism of berberine for myocardial fibrosis improvement of rats with myocardial infarction via Notch signaling pathway
Objective To investigate the effect of berberine on improving myocardial fibrosis in rats with myocardial infarction(MI).Methods Among the 60 rats,according to the random number table method,ten were chosen as the sham operation group,with the remaining 50 adopted to build an MI model by utilizing the coronary artery ligation method.Then,the 40 successfully modeled rats were divided into the model group,metoprolol group,low-dose berberine group,and high-dose berberine group,with ten rats in each group.After modeling for 48 hours,gavage administration was conducted with berberine on the high-dose(50 mg/kg)and low-dose(100 mg/kg)berberine groups,metoprolol(10 mg/kg)on the metoprolol group,and physiological saline(2 mL/d)on the sham operation group and model group.The treatment was carried out once a day for 30 days.Additionally,the body mass of each group was recorded,and the pathological changes of cardiac muscular tissue after HE staining were observed,with the collagen fiber content in cardiac muscular tissue detected by Sirius red staining.The matrix metalloproteinase-1(MMP-1)and MMP-9 proteins in cardiac muscular tissue were detected by immunohistochemistry staining,and the key proteins of the Notch pathway(Hey1 and Hes1),nerve growth factor(NGF),and α smooth muscle actin(α-SMA)proteins in cardiac muscular tissue were also detected by Western blotting.Results The model group had lower body mass at all time points than the sham operation group(P<0.05),and compared with the model group,the administration groups'body mass at all time points was higher(P<0.05).Meanwhile,there was no abnormal change in the cardiac muscular tissue of rats in the sham operation group.The cardiac muscular tissue of rats in the model group was disordered,and cardiac muscle cells had obvious degeneration and necrosis,with notable edema in intercellular substances and abundant inflammatory cell infiltration.The degeneration and necrosis of each treatment group were improved in treatment groups,with the most remarkable improvement in the high-dose berberine group.Compared with the sham operation group,the collagen fiber content in the cardiac muscular tissue of the model group was higher(P<0.05),while that of the metoprolol group,low-dose berberine group,and high-dose berberine group was lower than the collagen fiber content of the model group(P<0.05).Compared with the sham operation group,the expression of MMP-1 and MMP-9 proteins in the cardiac muscular tissue of rats in the model group was higher(P<0.05),while that of MMP-1 and MMP-9 proteins in the metoprolol group,high-dose berberine group and low-dose berberine group was lower than that of the model group(P<0.01).Compared with the sham operation group,the expression of Hes1,Hey1,NGF,and a-SMA proteins in the cardiac muscular tissue of rats in the model group was higher(P<0.05).Compared with the model group,the expression of Hes1,Hey1,NGF,and α-SMA proteins in the metoprolol group,high-dose berberine group,and low-dose berberine group was lower(P<0.01).Conclusion Berberine can inhibit myocardial fibrosis of MI rats via the Notch signaling pathway.
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