论文部分内容阅读
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 signaling pathway in doxorubicin-induced liver injury in mice and the effect of rosuvastatin on this pathway. Methods Thirty eight-week-old male C57BL / 6J mice were randomly divided into three groups. Rats in the intervention group were pretreated with rosuvastatin 10 mg / (kg · d) for 5 days. The rats in the intervention group were given adriamycin 15 mg / kg respectively to establish a liver injury model. The intervention group was given rosuvastatin for 5 days. Twenty-four hours after the last intragastric administration, all the mice were sacrificed and serum lipid and liver function were measured by semi-automatic biochemical analyzer. SOD and MDA contents in liver homogenate were also detected. HE staining was used to observe the morphological changes of liver cells in each group. , NF-κB expression. Results Compared with the control group, the levels of serum TC, TG, LDL-C, ALT and AST were significantly increased (P <0.05), HDL-C was significantly decreased <0.05). Hepatocellular swelling, vascular congestion and lymphocytic infiltration decreased Sirt1 expression and increased NF-κB (P <0.05). The levels of serum TC, TG, LDL-C, ALT and AST were significantly decreased (P <0.05), HDL-C was significantly increased (P <0.05) Structural integrity, inflammatory cells decreased, Sirt1 expression increased, NF-κB decreased (P <0.05). Conclusion Rosuvastatin can effectively protect doxorubicin-induced hepatotoxicity injury by regulating the expression of Sirt1 / NF-κB.