【摘要】 目的探讨裙带菜多糖（SPUP）治疗动脉粥样硬化（AS）并发非酒精性脂肪肝（NAFLD）的作用机制。方法以雄性ApoE^-/-小鼠为研究对象,采用高脂饮食诱导建立动脉粥样硬化并发非酒精性脂肪性肝病模型,随机分为正常组、模型组、阳性药组、裙带菜多糖低剂量组及裙带菜多糖高剂量组;测试血脂水平和肝功能状况;苏木精-伊红（HE）染色评估主动脉及肝脏病理状态;油红O染色判断肝脏脂肪损害程度;最后采用免疫组化及免疫荧光技术分析氧化应激相关蛋白在肝脏中的表达。结果与正常组比,模型组小鼠血脂、肝功能水平明显升高（P <0.01）,主动脉管腔斑块增多、狭窄率明显升高（P <0.01）,肝脏明显病变且脂肪油滴较多;而裙带菜多糖能调节血脂水平（P <0.05,P <0.01）,减少斑块形成,明显减轻管腔狭窄率（P <0.01）,改善肝脏病变状况且减少脂肪变性。此外,与正常组比,模型组小鼠肝脏中HO-1（P <0.01）和NQO1（P <0.05）表达明显降低,Keap1（P <0.01）和Nrf2（P <0.05）表达明显升高;而裙带菜多糖高剂量组小鼠Keap1表达明显降低（P <0.01）,Nrf2及其下游抗氧化蛋白HO-1和NQO1的表达明显上调（P <0.01）。结论裙带菜多糖能有效预防动脉粥样硬化并发非酒精性脂肪性肝病,其作用机制主要与激活Keap1-Nrf2/ARE信号通路、调节抗氧化应激反应有关。更多还原

【Abstract】 Objective The aim of this study was to evaluate the protective effect and mechanism of sulfated polysaccharides from Undaria pinnatifida（SPUP） on atherosclerosis（AS） complicated with nonalcoholic fatty liver disease（NAFLD）.Methods Male Apolipoprotein E-knockout(ApoE^-/-)mice were fed with high fat diet to induce AS complicated with NAFLD. Mice were randomly divided into normal group（NG）,model group（MG）,positive drug group（PG）,low-dose group（SLG）and high-dose group（SHG）. The levels of plasma lipids and liver function were measured. Hematoxylin-eosin（HE）staining was used to determine the pathological state of the liver and the aortic.And saturated oil red O staining was used to determine the degree of liver fat lesions. On this basis,the expression of oxidative stress-related proteins in the liver was analyzed by immunofluorescence and immunohistochemical techniques.Results Compared with NG,the levels of blood lipids and liver function in MG mice were significantly increased（P < 0.01）,plaques in the aortic lumen were increased,the stenosis rate increased significantly（P <0.01）, liver lessions and fat droplets were found more frequently. SPUP could regulate blood lipid levels（P < 0.05,P < 0.01）, reduce plaque formation, significantly reduce the rate of lumen stenosis（P < 0.01）, improve liver lessions and reduce steatosis. In addition,compared with NG,the expression of HO-1（P < 0.01）and NQO1（P <0.05）in the liver of MG mice was significantly reduced,and the expression of Keap1（P < 0.01）and Nrf2（P <0.05）was significantly increased. The expression of Keap1 in SHG mice was significantly reduced（P < 0.01）,and the expression of Nrf2 and its downstream antioxidant proteins HO-1 and NQO1 was significantly up-regulated（P <0.01）.Conclusion SPUP could effectively prevent AS complicated with NAFLD,and its effect on AS complicated with NAFLD is mainly related to activate Keap1-Nrf2/ARE signal pathway and regulate anti-oxidative stress reaction.更多还原