Abstract: Objective: To investigate the protective effect of paeonol on myocardial injury in the rats with heart failure, and to elucidate its preliminary pharmacological mechanism. Methods: The rat models of heart failure were replicated by intraperitoneal injection of doxorubicin. After successful modeling, the rats were randomly divided into model group(n=10), captopril group(n=11), low dose of paeonol group(n=11) and high dose of paeonol group(n=11), and the normal rats were used as control group(n=10).After successful modelring, the rats were given the drug continuously for 5 weeks, and the body weights of rats were recorded.After the last administration,the rats were anesthetized,and the changes of mean arterial pressure(MAP),heart rate(HR),left ventricular end diastolic pressure(LVEDP), left ventricular systolic blood pressure (LVSP), maximum rate of decrease of left ventricular blood pressure (-dp/dt_max), and maximum rate of increase of left ventricular blood pressure (+dp/dt_max)]of the rats were observed.The serum of rat orbital peripheral blood was isolated, and the levels of the serum tumor necrosis factor (TNF-β) and interleukin-6 (IL-6) were detected by ELISA. After anesthesia, 5 rats were randomly selected and the heart was obtained under aseptic operation; Western blotting method was used to detect the expression levels of Bax, B cell lymphoma - 2 (Bcl-2), cysteine aspartic acid protease 3 (Caspase-3), cysteine aspartic acid protease 8 (Caspase-8), cysteine aspartic acid protease 9 (Caspase-9) and cytochrome C (Cyt C) proteins in myocardium tissue of the rats in various groups. HE staining was used to observe the pathomorphology of myocardium tissue of the rats. Results: Compared with control group, the body weight of the rats in model group was significantly reduced (P<0.05),and MAP and LVEDP were increased(P<0.05), HR, LVSP, +dp/dt_max and -dp/dt_max were significantly decreased (P<0.05),the serum TNF-α and IL-6 levels were increased (P<0.01), the expression levels of Bax,Caspase-3,Caspase-8,Caspase-9 and Cyto-C proteins were significantly increased (P<0.01),and the expression level of Bcl-2 was significantly decreased (P<0.05). Compared with model group, the body weights of the rats in captopril,low and high doses of paeonol groups were significantly increased (P<0.05),the cardiac function indexes were improved significantly (P<0.05), the TNF-α and IL-6 levels were decreased (P<0.05), the expression levels of Bax, Caspase-3, Caspase-8, Caspase-9 and Cyto-C proteins in myocardium tissue of the rats were significantly decreased (P<0.05), and the Bcl-2 protein expression levels were increased significantly (P<0.05).The HE staining results showed that compared with control group, the myocardium tissue of the rats in model group was damaged obviously, and the myocardial cells were edema extensively. Compared with model group, the myocardial fiber arrangement and myocardial interstitial edema of the rats in captopril group and low and high doses of paeonol groups were significantly improved. Conclusion: Paeonol has a protective effect on the myocardium of the rats with heart failure, and the mechanism may be related to the improvement of hemodynamics, anti-inflammation and anti-apoptosis, and the protection of myocardial cells. High dose of paeonol is more effective in protecting the cardiac function and anti-apoptosis.

Key words: paeonol, adriamycin, heart failure, myocardial function, hemodynamics, disease model,animal