Effect of Ciwujia Injection on decrease of cardiac contractile function induced by doxorubicin hydrochloride / 中草药

ABSTRACT

Objective To investigate the protective effect of Ciwujia Injection (CI) on the decrease of cardiac contractile function induced by doxorubicin hydrochloride, and provide experimental basis for its clinical application. Methods The cardiotoxicity model in rats was established by ip injection of doxorubicin hydrochloride with a dose of 2.5 mg/kg every week for 6 weeks, and the total cumulative dose was 15 mg/kg. Rats were equally divided into five groups with 10 rats in each group (e.g. model group, three test groups of CI, positive group). In addition, a normal control group of 10 rats was injected intraperitoneally with normal saline (NS) once a week for 6 weeks. Normal control and model group were given NS intravenously. The test groups were given CI and the positive group was given Shenqi Fuzheng Injection. The CI and Shenqi Fuzheng Injection were infused by tail vein for 1 h when doxorubicin hydrochloride administrated. The parameters of left ventricular systolic function including ejection fraction (EF), shortening fraction (FS), the maximal rate of rise of left ventricular pressure (+LVdp/dtmax), and heart geometric shape were measured. Cardiomyocyte apoptosis was measured with immunohistochemistry, apoptosis-related protein and oxidative stress factors such as SOD, MDA, and LPO were measured with enzyme-linked immune sorbent assay, or chemical method. The ultrastructural changes of myocardium under electron microscope were observed. Results Compared with model group, after CI treatment (50, 100, and 200 mg/kg), the cardiac systolic function was improved; the declined EF, FS, and + LVdp/dtmax increased (P < 0.05, 0.01). The heart geometric shape was improved significantly with CI treatment, the expanded LVIDs and LVVs decreased (P < 0.05, 0.01). CI can inhibit myocardial cell apoptosis (P < 0.01), the myocardial apoptosis rate decreased (P < 0.01), and the Bax/Bcl-2 decreased (P < 0.01). In addition, CI (100 and 200 mg/kg) can decline the generation of LPO, MDA and increase the activity of SOD. Conclusion CI can effectively relieve cardiotoxicity induced by doxorubicin hydrochloride in rats, increase cardiac function, improve the cardiac configuration, and reduce the damage of myocardial ultrastructure. The mechanism may be related to decreasing oxidative stress and inhibition of apoptosis in impaired myocardial cells.