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Objective: To compare the therapeutic effects of Astragaloside and Perindopril on myocardial sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity and the SERCA type 2 mRNA level in Coxsackievirus B3 (CVB3)-infected cardiomyocytes. Methods: Cultured cardiomyocytes of rats were divided into normal, model, Astragaloside and Perindopril groups. The model, Astragaloside and Perindopril groups were infected with CVB3. Meanwhile， the Astragaloside and the Perindopril groups were treated with Astragaloside (10 μg/ml) and Perindopril (1.3 μg/ml) respectively. Cytopathic effect (CPE), cardiac troponin I ( cTnI) , the SERCA activity and mRNA level of the SERCA type 2 were observed after 96 hours. Results: The CPE and cTnI of model group were significantly higher than those of normal, Astragaloside and Perindopril groups (P<0.01). The activity and the mRNA expression of myocardial SERCA of model group were significantly lower than those of normal, Astragaloside and Perindopril groups (P<0.01-0.05). Compared with Astragaloside group, the CPE, cTnI of Perindopril group were higher and the activity and mRNA level of Perindopril group were lower. But there were no significant difference between the two groups (P>0.05). Conclusion: Astragaloside and Perindopril were able to reverse the down-regulations of cardiac SERCA activity and mRNA expression caused by virus infection to alleviate the cardiomyocyte injury.