[Neuroprotective effect of ginsenoside Rb-1 on a rat model of Alzheimer's disease].

Objective: To investigate the protective mechanism of ginsenoside Rb-1 on the brain in a rat model of Alzheimer's disease. Methods: Fifty-six male Sprague-Dawley rats were randomly divided into control group, model group, low-dose Rb-1 group (Rb-1: 25 mg•kg(-1)•d(-1)) and high-dose Rb-1 group (Rb-1:50 mg•kg(-1)•d(-1)). Morris water maze was designed to observe the changes of learning and memory ability in rats. Flow cytometry was used to detect the apoptosis of hippocampal neurons. Immunohistochemistry and Western blot were employed to detect the expression levels of apoptosis-related genes (p53, Bax, cytochrome C (Cyto C), Caspase-3 and caspase-9) and anti-oxidative stress-associated genes (nuclear Factor-E2-related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (keap-1), heme oxygenase 1(HO-1) and NADPH quinone dehydrogenase 1 (NQO1)).The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected by relevant kits. ANOVA and Tukey-Kramer test were used for statistical analysis. Results: The learning and memory ability of rats in the model group was lower than that of the control group (P<0.01).The learning and memory ability of rats in the high-dose Rb-1 treatment group was significantly higher than that of the model group [(80±8) s vs (100±11) s, t=5.390, P<0.01]. The expression levels of apoptosis-related genes (p53, Bax, Cyto C, caspase-3 and caspase-9) in the model group were significantly higher than those in the control group (P<0.01), while the expression levels of these genes in low-dose and high-dose Rb-1 groups were significantly lower than those of the model group (P<0.01). The expression levels of Nrf2, HO-1 and NQO1 genes in the model group were significantly lower than those in the control group (P<0.05), while the expression of these genes in low-dose and high-dose Rb-1 groupswere significantly higher than those of the model group (P<0.01). The activities of CAT, GSH-Px and SOD in the model group were lower than those in the control group (P<0.01), however the activities of CAT, GSH-Px and SOD in low-dose and high-dose Rb-1 groups were higher than those of model group (P<0.05). Conclusions: Both low-dose and high-dose Rb-1 have protective effect on memory and cognitive function of Alzheimer's disease rats by reducing the damage and apoptosis of hippocampal neurons, down-regulating the expression levels of p53, Bax, Cyto C, caspase-3 and caspase-9, up-regulating the expression of Nrf2, HO-1 and NQO1 genes, and increasing the activities of CAT, GSH-Px and SOD. Moreover, the protective effect of Rb-1 on rat brain may be dose-dependent.目的： 探讨人参皂苷Rb-1对阿尔茨海默病（AD）模型大鼠大脑保护的作用机制。 方法： 选取SD雄性大鼠56只，按照随机数字表法分为对照组、模型组、Rb-1低剂量组（Rb-1 25 mg·kg(-1)·d(-1)）、Rb-1高剂量组（Rb-1 50 mg·kg(-1)·d(-1)），每组14只。通过Morris水迷宫实验观察大鼠学习记忆能力的改变，应用流式细胞术检测大鼠海马神经元的凋亡；通过免疫组化及Western印迹检测凋亡相关基因p53、Bax、Cyto C、caspace-3、caspace-9，及抗氧化应激相关基因Nrf2 、keap-1、血红素加氧酶1（HO-1）、NADPH醌氧化还原酶（NQO1）的蛋白表达水平；应用试剂盒检测抗氧化酶过氧化氢酶（CAT)、谷胱甘肽过氧化物酶（GSH-Px)、超氧化物歧化酶（SOD）的活性。应用方差分析及Tukey-Kramer检验进行统计分析。 结果： 模型组大鼠学习记忆能力低于对照组大鼠（P<0.01）；Rb-1高剂量组学习记忆能力均明显高于模型组[(80±8) s比（100±11) s,t=5.390, P<0.01]。凋亡相关基因p53、Bax、Cyto C、caspace-3、caspace-9在模型组大鼠表达明显高于对照组（P<0.01），Rb-1低剂量组及Rb-1高剂量组表达明显低于模型组（P<0.01）。模型组大鼠Nrf2、HO-1、NQO1的表达明显低于对照组（P<0.05），Rb-1低剂量组及Rb-1高剂量组表达明显高于模型组（P<0.01）。模型组抗氧化酶CAT、GSH-Px、SOD的表达活性低于对照组（P<0.01），Rb-1低剂量组及Rb-1高剂量组活性高于模型组（P<0.05）。 结论： Rb-1低剂量组及Rb-1高剂量组对AD模型大鼠记忆力及认知功能具有保护作用，可以降低海马神经元的损伤和凋亡，并通过下调p53、Bax、Cyto C、caspace-3、caspace-9蛋白的表达水平，上调Nrf2、HO-1、NQO1的表达以及增加抗氧化酶CAT、GSH-Px、SOD的活性发挥作用。Rb-1对大鼠大脑的保护作用可能呈剂量相关性。.