肉苁蓉多糖对D-半乳糖致衰老模型小鼠CREB表达的影响

目的:观察肉苁蓉多糖(CDPS)对D-半乳糖致衰老模型小鼠学习记忆的影响及可能的机制。方法:昆明种小鼠90只,随机分为6组,即正常对照组,模型组,CDPS低、中、高剂量组(25,50,100 mg·kg-1),阳性对照组,每组15只。模型组、CDPS组及阳性对照组皮下注射150 mg·kg-1的D-半乳糖建立衰老小鼠模型,正常对照组给予等量生理盐水;同时,CDPS各组灌胃给予相应浓度的CDPS药液,阳性对照组给予10 mg·kg-1吡拉西坦,正常对照组及模型组给予等量蒸馏水。连续给药6周后,采用水迷宫、跳台实验测定小鼠学习记忆能力;试剂盒检测小鼠脑组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量;HE染色观察脑组织海马区神经元细胞形态学变化;免疫组织化学染色检测cAMP反应元件结合蛋白(CREB)的表达水平。结果:在水迷宫实验中,各给药组与模型组比较,逃避潜伏期和第1次到达站台时间均明显缩短且穿越站台次数增加(P<0.05)。在跳台实验中,与模型组比较,各给药组小鼠下台潜伏期显著延长,错误次数减少(P<0.05)。与模型组比较,各给药组小鼠脑组织SOD活性增加,MDA含量下降(P<0.05)。与模型组比较,各给药组小鼠脑组织海马CA1区神经元数量增加,病理改变减轻;各给药组小鼠海马区CREB表达水平与模型组比较显著增加(P<0.05)。结论:肉苁蓉多糖可以改善D-半乳糖致衰老模型小鼠的学习记忆能力,其机制可能与上调CREB表达有关。

Effect of Cistanche deserticola Polysaccharides on Expression of CREB in D-galactose Induced Aging Model Mice

Objective: To study the effect of Cistanche deserticola polysaccharides herb (CDPS) on learning and memory ability of D-galactose(D-gal) induced aging mice and possible mechanisms. Method: Ninety mice were randomly assigned into control group, model group, CDPS low, middle and high dose group (25, 50, 100 mg·kg^-1), positive control group, 15 mice in each group. The model, CDPS and positive control groups were injected 150 mg·kg^-1 D-gal subcutaneously to establish aging-mouse model, and the control group was given the same volume of saline water;meanwhile, the CDPS groups were administered orally corresponding concentrations of CDPS liquid and positive control group was given 10 mg·kg^-1 piracetam, while the control and the model groups were given the same volume of distilled water.After six weeks of continuous administration, the water maze performance and step-down passive avoidance test were applied to determine learning and memory ability of mice. Moreover, superoxide dismutase(SOD) activity and malondialdehyde(MDA) content in brain tissue of mice were detected by kits. Morphological changes of neurons in the hippocampus of brain tissue were observed with HE staining. Furthermore, the expression level of cAMP response element binding protein(CREB) was examined by immunohistochemistry. Result: In water maze performance, CDPS(25, 50, 100 mg·kg^-1) significantly decreased latency and the first time arrived platform and increased travel times in D-gal-treated mice. In step-down passive avoidance test, the step down latencywas significantly prolonged and the number of errors was decreased in CDPS(25, 50, 100 mg·kg^-1)groupcompared to those in the D-gal-control group. In addition, CDPS(25, 50, 100 mg·kg^-1) significantly increased the activity of SOD and decreased the level of MDA in the brain tissues of D-gal-treated mice. At the same time, CDPS increased the number of neuron in hippocampal CA1 of mouse brain and ameliorated the pathological changes according to HE staining and CDPS(25, 50, 100 mg·kg^-1) increased CREB expression levels in the hippocampus of mice comparing with those in D-gal-control group. Conclusion: CDPS canimprove the learning and memory ability of D-gal induced aging model mice, and the mechanism may be related to increasing CREB expression.