【摘要】 目的观察白藜芦醇(RV)对高脂饮食(HFD)诱导的认知功能障碍的影响。方法 60只雄性C57BL/6J小鼠随机分为对照组、高脂喂养组(HFD组)、HFD+30 mg/kg RV组(30 mg/kg RV组),HFD+67. 5 mg/kg RV组(67. 5 mg/kg RV组)和HFD+135 mg/kg RV组(135 mg/kg RV组),每组10只,共干预7个月。于干预结束后,检测小鼠的体质量和血脂水平。采用Morris水迷宫和新物体识别实验评价学习记忆水平。采用ELISA检测海马区IL-1β、TNF-α、超氧化物歧化酶(SOD)和丙二醛(MDA)水平。采用Western boltting法检测海马区沉默信息调节因子1(SIRT1)通路表达。采用免疫荧光染色检测海马CA1区SIRT1蛋白水平。结果 (1)与HFD组比较,30 mg/kg RV组第4～6个月体质量及三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平显著降低,高密度脂蛋白胆固醇(HDL-C)水平显著增高(P <0. 05～0. 01); 67. 5 mg/kg RV组第4～6个月体质量及总胆固醇(TC)、TG、LDL-C水平显著降低,HDL-C水平显著增高(均P <0. 01); 135 mg/kg RV组第2～7个月体质量及TC、TG、LDL-C水平显著降低,HDL-C水平显著增高(P <0. 05～0. 01)。与135 mg/kg RV组比较,30 mg/kg RV组TC、TG、LDL-C水平显著增高,HDL-C水平显著降低(均P <0. 01);67. 5 mg/kg RV组TC、TG水平显著增高(均P <0. 05)。与67. 5 mg/kg RV组比较,30 mg/kg RV组TC、TG、LDL-C水平显著增高,HDL-C水平显著降低(P <0. 05～0. 01)。(2)与HFD组比较,30 mg/kg RV、67. 5 mg/kg RV、135 mg/kg RV组相对识别指数(DI)、穿越平台次数、第5 d进入平台时间显著升高(P <0. 05～0. 01)。与135 mg/kg RV组比较,30 mg/kg RV组DI显著降低(P <0. 01)。与67. 5 mg/kg RV组比较,30 mg/kg RV组DI显著降低(P <0. 01)。(3)与HFD组比较,30 mg/kg RV、67. 5 mg/kg RV、135 mg/kg RV组TNF-α、IL-1β、MDA水平显著降低,SOD水平显著增高(P <0. 05～0. 01)。与135 mg/kg RV组比较,30 mg/kg RV组TNF-α、IL-1β水平显著增高(均P <0. 01)。与67. 5 mg/kg RV组比较,30 mg/kg RV组TNF-α、IL-1β水平显著增高(均P <0. 05)。(4)与HFD组比较,30 mg/kg RV、67. 5 mg/kg RV、135 mg/kg RV组SIRT1水平显著升高,乙酰化p53(Ac-p53)、乙酰化核因子-κB(Ac-NF-κB)和乙酰化Forkhead转录因子(Ac-FoxO1)水平显著降低(P <0. 05～0. 01)。与135 mg/kg RV组比较,30 mg/kg RV组SIRT1水平显著降低,Ac-p53、Fox O1和AcNF-κB水平显著升高(P <0. 05～0. 01)。与67. 5 mg/kg RV组比较,30 mg/kg RV组Ac-p53水平显著升高(P <0. 05)。结论 RV具有浓度效应,可以减少小鼠HFD引起的认知障碍损伤,其机制可能与抑制炎症和氧化应激反应,以及促进SIRT1通路的表达有关。更多还原

【Abstract】 Objective To investigate the effect of resveratrol( RV) against cognitive impairment induced by high fat diet( HFD). Methods Sixty male C57 BL/6 J mice were randomly divided into control group,high fat diet( HFD) group,HFD + 30 mg/kg RV group( 30 mg/kg RV group),HFD + 67. 5 mg/kg RV group( 67. 5 mg/kg RV group) and HFD + 135 mg/kg RV group( 135 mg/kg RV group). There were 10 mice in each group,and all interventions took place for 7 months. After intervention,the body weight and serum lipid levels were valued. The cognitive development were examined by Morris water maze and novel object recognition paradigm test. The levels of TNF-α,IL-1β,superoxide dismutase( SOD) and malondialdehyde( MDA) of hippocampus were assessed by ELISA. The expression of silent information regulator 1( SIRT1) pathway was investigated by Western blotting. The expression of SIRT 1 in the CA 1 area of hippocampus was determined by immunofluorescence. Results( 1)Compared with those in HFD group,body weight in 4-6 month and the expressions of triglycerides( TG),low density lipoprotein cholesterol( LDL-C) in the 30 mg/kg RV group were significantly decreased,and the level of high density lipoprotein cholesterol( HDL-C) was significantly increased( P < 0. 05-0. 01). Compared with those in HFD group,body weight in 4-6 month and the expressions of TC,TG,LDL-C in the 67. 5 mg/kg RV group were significantly decreased,and the level of HDL-C was significantly increased( all P < 0. 01). Compared with those in HFD group,body weight in 2-7 month and the expressions of total cholesterol( TC),TG,LDL-C in the 135 mg/kg RV group were significantly decreased,and the level of HDL-C was significantly increased( P < 0. 05-0. 01).Compared with those in 135 mg/kg RV group,the expressions of TC,TG,LDL-C in the 30 mg/kg RV group were significantly increased,and the level of HDL-C was significantly decreased( all P < 0. 01). Compared with those in135 mg/kg RV group,the expressions of TC,TG in the 67. 5 mg/kg RV group were significantly increased( all P <0. 05). Compared with those in 67. 5 mg/kg RV group,the expressions of TC,TG,LDL-C in 30 mg/kg RV group were significantly increased,and the level of HDL-C was significantly decreased( P < 0. 05-0. 01).( 2) Compared with those in HFD group,entries time at 5 th day,entries number and relative discrimination index( DI) in 30 mg/kg RV group,67. 5 mg/kg RV group and 135 mg/kg RV group( P < 0. 05-0. 01). Compared with that in 135 mg/kg RV group,DI in 30 mg/kg RV group was significantly decreased( P < 0. 01). Compared with that in 67. 5 mg/kg RV group,DI in the 30 mg/kg RV group was significantly decreased( P < 0. 01).( 3) Compared with those in HFD group,the expressions of TNF-α, IL-1β and MDA were significantly decreased, and the level of SOD was significantly increased in 30 mg/kg RV group,67. 5 mg/kg RV group and 135 mg/kg RV group( P < 0. 05-0. 01).Compared with those in 135 mg/kg RV group,the levels of TNF-α,IL-1β were significantly increased in the30 mg/kg RV group( all P < 0. 01). Compared with those in 67. 5 mg/kg RV group,the levels of TNF-α,IL-1βwere significantly increased in 30 mg/kg RV group( all P < 0. 05).( 4) Compared with those in HFD group,the expression of SIRT1 were significantly increased,and the levels of acetylated-p53( Ac-p53),acetylated-FoxO1( AcFox O1),acetylated-nuclear factor-kappa B( Ac-NF-κB) were significantly decreased in the 30 mg/kg RV group,67. 5 mg/kg RV group and 135 mg/kg RV group( P < 0. 05-0. 01). Compared with those in 135 mg/kg RV group,the expression of SIRT1 was significantly decreased,and the levels of Ac-p53,Fox O1,Ac-NF-κB were increased in30 mg/kg RV group( P < 0. 05-0. 01). Compared with that in 67. 5 mg/kg RV group,the expression of Ac-p53 was significantly increased in 30 mg/kg RV group( P < 0. 05). Conclusion RV has concentration effect,and it can attenuate cognition impairment induced by HFD through its antioxidant and anti-inflammatory function related to SIRT1 signaling pathway.更多还原