目的探讨蝙蝠葛碱(DAU)对阿尔茨海默病(AD)小鼠海马晚期糖基化终产物受体(RAGE)和核转录因子(NF)-κBp65的影响。方法雄性小鼠随机分成对照组、模型组、多奈哌齐组(0.001 g/kg)及DAU高、中、低剂量组(2.4、1.2、0.6 g/kg)。小鼠双侧海马微量注射β-淀粉样蛋白(Aβ)(1~42)(2 g/L)和腹腔注射D-半乳糖(180 mg/kg)诱导AD小鼠,连续治疗35 d后取材。采用Morris水迷宫(MWM)检测AD小鼠学习记忆能力,酶联免疫吸附(ELISA)检测海马白细胞介素(IL)-1β、IL-6含量,免疫组化(IHC)、实时定量(RT)-PCR和Western印迹检测海马RAGE和NF-κBp65表达。结果与模型组比较,DAU高、中剂量明显改善AD小鼠学习记忆能力,明显降低海马IL-1β、IL-6、RAGE和NF-κBp65水平(均P〈0.05)。结论 DAU通过抑制海马RAGE和NF-κBp65表达来改善AD小鼠学习记忆能力,以此在AD治疗中发挥重要作用。
Objective To explore the effects of dauricine( DAU) on receptor for advanced glycation end products( RAGE) and nuclear transcription factor( NF)-κBp65 of the hippocampus in Alzheimer's disease( AD) mice. Methods Male mice were randomly divided into control,model,donepezil( 0.001 g/kg),DAU high-dose( 2.4 g/kg),DAU medial-dose( 1.2 g/kg),DAU low-dose( 0.6 g/kg) groups.The AD model mice were induced by microinjection of incubated amyloid beda91 ~ 42)( 2 g/L) into the dorsal blade of and intraperitoneal injection of D-galactose( 180 mg/kg) in the dentale gyrus in the bilateral hippocampus. Morris water maze was used to observe the learning and memory ability of AD mice. Enzyme-linked immunosorbent assay( ELISA) was used to determine the contents of IL-1β and IL-6. By immunohistochemistry( IHC),real time( RT)-PCR and Western bolt were used to test the contents of RAGE and NF-κBp65 of the hippocampus in AD mice.Results Compared with those of model group,DAU high-dose and medial-dose significantly improved the learning and memory ability of AD mice( P〈0.05). DAU high-dose and medial-dose decreased the levels of IL-1β,IL-6,RAGE and NF-κBp65 in the hippocampus( P〈0.05).Conclusions DAU could improve the ability of learning and memory of AD mice. DAU plays a certain role in the treatment of AD through inhibiting RAGE and NF-κBp65.