Abstract: Objective To investigate the expression of monocyte chemoattractant protein 1 (MCP-1) in doxorubicin induced myocardial injury in SD rats and its potential intervention mechanism. Methods　Thirty male Sprague-Dawley (SD) rats aged 8 weeks with special pathogen free (SPF) animal grade were randomly divided into three groups: control group (Con group, n=10, gavage and intraperitoneal injection of saline solution), doxorubicin group (Dox group, n=10, intraperitoneal injection of 1.25 mL/kg doxorubicin + gavage of 2 mL/kg saline solution) and valsartan + doxorubicin group (Val+Dox group, n=10, intraperitoneal injection of 1.25 mL/kg doxorubicin + gavage of 2 mL/kg valsartan). After treatment for six weeks, the changes of cardiac function were detected by echocardiography. Myocardial tissue samples were collected for observing the myocardial ultrastructure under electron microscopy. The protein level of serum MCP-1, regulatory and activation of normal T cell expression and secretion factors (RANTES) and secondary lymphoid organ chemokine (6Ckine) were detected by protein chip technology. The expressions of MCP-1 in myocardial tissue samples were tested by Western blot assay. Results　Echocardiography indicated that compared with Con group, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were significantly decreased in the other two groups, while the left ventricular end-diastolic dimension (LVESD) and left ventricular end-diastolic dimension (LVEDD) were obviously increased (P＜0.05). On the other hand, in comparison with Dox group, LVEF and LVFS were significantly increased in Val+Dox group, while LVESD and LVEDD were significantly decreased in Val+Dox group (P＜0.05).Under the electron microscope,the ultrastructure of myocardial cells was clear in the Con group, and the myocardial structure was dim, autophagic body was observed in the Dox group. In the Val+Dox group, the myocardial structure was blurred, the size of mitochondria was increased, and intact and swollen mitochondria were found to have different sizes. Compared with the Con group, the protein levels of MCP-1，RANTES and 6Ckine were up-regulated 1.87, 1.40 and 1.26-fold in Dox group (P＜0.05). Western blot assay displayed that the protein expression of MCP-1 was significantly higher in the Dox group than that of Con group (P＜0.05), and the protein expression of MCR-1 was significantly lower in the Dox group than that in the Val+Dox group (P＜0.05). Conclusion MCP-1 may be associated with doxorubicin induced myocardial injury, and valsartan may protect myocardial tissue from doxorubicin induced myocardial injury through down-regulating the expression of MCP-1.

Key words: doxorubicin, cardiotoxicity, valsartan, rats, Sprague-Dawley, chemokine CCL2；monocyte chemoattractant protein1