Study on astragaloside Ⅳ alleviating the cardiotoxicity caused by doxorubicin by inhibiting MerTK

ObjectiveTo investigate the effects and mechanism of astragaloside Ⅳ on the doxorubicin-induced myocardial injury.

MethodsThe 6-week-old ICR male mice were randomly divided into the control group, doxorubicin group, doxorubicin+Astragaloside Ⅳ group.The control group was given a single intraperitoneal injection of 0.9% sodium chloride solution, and the other groups were given a single intraperitoneal injection of 20 mg/kg doxorubicin for modeling.The doxorubicin+astragaloside Ⅳ 80 mg/kg group were given astragaloside Ⅳ once a day by gavage, and the other groups were given a solvent(0.5% sodium carboxymethyl cellulose) by gavage for 10 days.On the 10th day, the mice's myocardial function(ejection fraction and fractional shortening) were detected using the echocardiography, and the heart rate of mice were monitored by the electrocardiogram test.On the 10th day, the serum and heart tissue of mice were collected, and the changes in the myocardial tissue structure were detected using Masson staining, and the levels of lactate dehydrogenase(LDH) and creatine kinase(CK-MB) were detected using biochemistry.The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in mice were examined using ELISA, and the protein levels of Mer tyrosine kinase(MerTK) in the myocardium were detected using Western blotting.

ResultsCompared with the control group, the heart rate and QT interval were significantly slower(P < 0.01), the cardiac ejection fraction and fractional shortening significantly decreased(P < 0.01), the contents of myocardial enzyme CK-MB and LDH significantly increased(P < 0.01), the protein expression lev el of p-MerTK significantly increased(P < 0.01), the levels of IL-1β, IL-6 and TNF-α significantly increased(P < 0.01), and there was severe fibrosis in the interstitium of mouse myocardial cells in adriamycin group.Compared with the doxorubicin group, the QT interval was significantly shortened(P < 0.01), the heart rate was improved almost to the normal level, the decreasing of cardiac ejection fraction and fractional shortening was significantly improved(P < 0.01), the contents of myocardial enzyme CK-MB and LDH significantly decreased(P < 0.01), the expression level of p-MerTK significantly decreased(P < 0.01), the levels of IL-1β, IL-6 and TNF-α significantly decreased(P < 0.01), and the area of myocardial fibrosis was significantly reduced in doxorubicin+astragaloside Ⅳ 80 mg/kg group.

ConclusionsAstragaloside Ⅳ may reduce the myocardial injury and cardiotoxicity induced by doxorubicin through inhibiting MerTK cleavage.