Rosuvastatin Up-regulating The Expression Of Sirt1/NF-?B Signal Pathway And Inhibiting Doxorubicin-induced Cardiotoxicity Injury In Experimental Mice

Objective To observe the effects of oxidative stress injury in mice myocardial followed by intra-peritoneal injection of doxorubicin(DOX); and to investigate the effects of rosuvastatin for up-regulating the expression of Sirt1/NF-?B signal pathway and inhibiting doxorubicin(DOX)-induced cardiotoxicity injury in experimental mice.Methods A total of 30 male C57 mice at(4-6) weeks of age were randomly divided into 3 groups. Treatment group, the mice received intra-gastric rosuvastatin 10mg/(kg.day) for 7 days, followed by intra-peritoneal injection of DOX 15mg/kg to induce the cardiotoxicity injury, and then received rosuvastatin for another 5 days. Model group, the mice received intra-peritoneal injection of DOX 15mg/kg to induce the cardiotoxicity injury, and then received intra-gastric normal saline for the same volume. Control group, the mice received intra-gastric normal saline for the same volume. n=10 in each group. The mice were killed at 12 days after treatment.The pathological change in myocardial tissue was observed by HE staining, the myocardial oxidative stress indexes of malonadehyde(MDA) level and super oxide dismutase(SOD) activity were measure by the operating kits and the protein expression of Sirt1/NF-?B was examined by immunohistochemistry.Results 1.Compared with Control group, Model group had obviously increased levels of MDA, NF-?B and decreased SOD activity, Sirt1 level, all P<0.05; the mice in Model group showed disordered myocardial structure with inflammatory cell infiltration.2. Compared with Model group, Treatment group had obviously decreased levels of MDA, NF-?B(while they were still higher than Control group), and increased SOD activity, Sirt1 level, all P<0.05; the mice in Treatment group showed intact myocardial structure with much less edema and lymphocyte infiltration.Conclusion 1. The mice received intra-peritoneal injection of DOX 15mg/kg can induce the cardiotoxicity injury, Sirt1/NF-?B signal pathway was involved in DOX-induced cardiotoxicity injury in experimental mice.2. Rosuvastatin can protect oxidative stress injury in mice myocardial by obviously decreased levels of MDA and increased SOD activity,It can also protect the injury via up-regulating the expression of Sirt1/NF-?B signal pathway.3. It's significative to take rosuvastatin for the cancer complicated with coronary heart disease during adriamycin chemotherapy.