Effect Of Rosuvastatin On Regulating Sirt1/NF-κB Signal Pathway In Mice With Doxorubicin-induced Hepatic Injury

Objective:To observe the effects of oxidative stress injury in mice liver followed by intra-peritoneal injection of doxorubicin,and to investigate the effects of rosuvastatin on regulating the expression of Sirt1/NF-κB signal pathway in doxorubicin-induced mice hepatotoxicity damage.Methods:30 male 8 weeks old C57BL/6J mice were randomly divided into 3 groups(n=10).Control group,the mice received intra-gastric normal saline for the same volume. Model group, the mice received intra-peritoneal injection of doxorubicin(15mg/kg) to build hepatotoxicity damage model, and then received intragastric normal saline for the same volume. Intervention group,the mice were pre-intragastric rosuvastatin(10mg/kg/day) for 5 days, followed by a single intra-peritioneal injection doxorubicin(15mg/kg) once, and then post-intervention for another 5 days.The mice were killed at 10 th day after treatment.TC、TG、LDL-C、HDL-C、ALT and AST were detected with full-automatic biochemical instrument, the hepatic oxidative stress indexes of malonadehyde(MDA) content and super oxide dismutase(SOD) activity were measured by the operating kits.HE staining for histopathological analysis in the liver were performed under the microscope and the protein expression of Sirt1/NF-κB was examined by immunohistochemistry.Results:1.Compared with control group, increased TC、TG、 LDL-C、MDA and NF-κB levels were observed in model group,HDL-C 、 SOD and Sirt1 decreased( P<0.05). Histopathological studies showed that doxorubicin caused hepatic structural injuries, such as cell swell, vascular congestion,inflammatory cell infiltration in the liver.2.Compared with model group,intervention group showed TC、TG、 LDL-C、MDA and NF-κB levels obviously decreased,and increased HDL-C、SOD and Sirt1(P<0.05). The mice in treatment group showed intact myocardial structure with much less edema and inflammatory cell infiltration.Conclusion:1.The mice received intra-peritoneal injection of doxorubicin 15mg/kg can cause the hepatotoxicity damage,Sirt1/NF-κB signal pathway was involved in doxorubicininduced hepatotoxicity injury in experimental mice.2.Rosuvastatin can protect oxidative stress injury against mice hepatotoxicity by obviously decreased the level of MDA and increased SOD activity,it can also protect against the liver injury via up-regulating Sirt1 expression and inhibiting NF-κB signal pathway.3.Patients need chemotherapy,it’s significant to administrate rosuvastatin to intervene liver damage at the early stage.