摘要
目的探讨Sirt1/NF-κB信号通路在阿霉素诱导小鼠肝脏损伤中的作用及瑞舒伐他汀对该通路的干预效果。方法 30只8周龄雄性C57BL/6J小鼠,随机分为3组。干预组预先给予瑞舒伐他汀悬液10 mg/(kg·d)5d,与模型组分别给予阿霉素15 mg/kg建立肝脏损伤模型,干预组继续瑞舒伐他汀干预5 d。末次灌胃24 h后处死全部小鼠,半自动生化仪检测血清血脂、肝功能;同时检测肝组织匀浆SOD、MDA含量;HE观察各组小鼠肝脏细胞形态变化;免疫组化法检测肝脏Sirt1、NF-κB的表达。结果与对照组相比,模型组血清TC、TG、LDL-C、ALT、AST明显升高(P<0.05),HDL-C显著降低(P<0.05),匀浆MDA增多,SOD降低(P<0.05),肝细胞肿胀,血管拥挤,淋巴细胞浸润,Sirt1表达减少,NF-κB增加(P<0.05)。干预组较模型组血清TC、TG、LDL-C、ALT、AST明显降低(P<0.05),HDL-C明显升高(P<0.05),SOD增多,MDA降低(P<0.05),肝细胞结构完整、炎细胞减少,Sirt1表达增加,NF-κB降低(P<0.05)。结论瑞舒伐他汀通过调控Sirt1/NF-κB表达,有效保护阿霉素诱导的肝脏毒性损伤。
Objective To investigate the role of Sirt1 / NF-κB signal pathway in doxorubicin（ DOX）-induced mice hepatotoxity damage and the effect of Rosuvastatin（ Ros） on this pathway. Methods Thirty male,8 weeks old,C57 BL /6J mice were randomly divided into 3 groups（ n = 10）. In DOX-treated group,the mice received intra-peritoneal injection of DOX（15 mg/kg）to build hepatotoxicity damage model,and then received intragastric normal saline for the same volume. DOX/Ros group,the mice were pre-intragastric Ros 10 mg /（ kg·d） for 5 d,followed by a single intra-peritioneal injection DOX（15 mg/kg）,and then post-intervention for another 5 d. Serum lipid and liver function were detected with semi-automatic biochemical instrument. The expression of SOD,MDA,Sirt1 and NF-κB were evaluated with immunohistochemical method. The morphological changes of the liver cells were observed with HE staining. Results When compared with the control group,the levels of TC,TG,LDL-C,ALT,AST and MDA in the model group were significantly increased,but LDL-C and SOD were decreased（ P〈0. 05）,and hepatocytes swelled,blood vessels congested with lymphocytic infiltration. The expression of Sirt1 in the model group significantly decreased,NF-κB significantly increased（ P〈0. 05）. Compared with the model group,the levels of TC,TG,LDL-C,ALT,AST and MDA in the intervention group significantly decreased whereas HDL-C and SOD increased（ P〈0. 05）,andhepatocytes arranged orderly. The expression of Sirt1 markedly increased,NF-κB decreased（ P〈0. 05）. Conclusion Rosuvastatin has protective effect against DOX-induced hepatotoxicity by up-regulating Sirt1 and inhibiting NF-κB.
出处
《中华全科医学》
2016年第4期533-535,539,共4页
Chinese Journal of General Practice
基金
山东省自然科学基金面上项目(ZR2010HM084)
