Rosuvastatin Up-regulating the Expression of Sirt1/NF-κB Signal Pathway and Inhibiting Doxorubicin-induced Cardiotoxicity Injury in Experimental Mice
10.3969/j.issn.1000-3614.2014.12.017
- VernacularTitle:瑞舒伐他汀上调沉默信息调节因子2相关酶1/核转录因子-κB信号通路抑制阿霉素所致的心肌损伤的研究
- Author:
Zhenchuang XI
;
Zhiyun WANG
- Publication Type:Journal Article
- Keywords:
Doxorubicin;
Sirt1signal pathway;
Cardiotoxicity injury;
Rosuvastatin
- From:
Chinese Circulation Journal
2014;(12):1029-1033
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effects of rosuvastatin for up-regulating the expression of Sirt1/NF-κB signal pathway and inhibiting doxorubicin (DOX)-induced cardiotoxicity injury in experimental mice.
Methods: A total of 30 male C57 BL/6J mice at (4-6) weeks of age were randomly divided into 3 groups. Treatment group, the mice received intra-gastric rosuvastatin 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-κB was examined by immunohistochemistry.
Results: Compared with Control group, Model group had obviously increased levels of MDA, NF-κB and decreased SOD activity, Sirt1 level, all P<0.05;the mice in Model group showed disordered myocardial structure with inlfammatory cell inifltration. Compared with Model group, Treatment group had obviously decreased levels of MDA, NF-κB (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 inifltration.
Conclusion: Sirt1/NF-κB signal pathway was involved in DOX-induced cardiotoxicity injury in experimental mice, rosuvastatin could protect the injury via up-regulating the expression of Sirt1/NF-κB signal pathway.
