巴戟天低聚糖对AD动物模型的神经保护作用及机制研究

In traditional Chinese medicine, it is believed that “kidneys storing essence，help producing bone marrow” and “the brain needs the support of bone marrow”. That is why there's the idea of “nurturing the kidney is good for the brain”. Prophase research have shown that the oligosaccharides of Morinda officinalis (OMO) play a useful role in improving the learning and memory ability of dementia rats and also have protective effect against neurons. In order to further reveal the neuroprotective mechanism of OMO，the project was based on the relationship of “brain disease in traditional Chinese medicine” and Alzheimer's disease, both of which have the common pathological features such as the abnormal cholinergic level, oxidative stress reaction, excitatory toxicity, abnormal expression of related gene and protein. D-galactose and Aβ25-35 would be used in inducing AD rat models. Morris water maze, HPLC-ECD and enzyme-labelled method would be used to Investigate the behavior, the neurotransmitter level, oxidative stress level, energy metabolism level and cholinergic level. Moreover, the expression level of related gene and protein such as Aβ, tau, SYP, BAX, NF-κB 65 and Capase-3 would be tested by RT-PCR and Western-blot. The project was intended to reveal the neuroprotective mechanism of OMO and provide scientific basis for statement of “nurturing the kidney is good for the brain” in traditional Chinese medicine.

中医有“肾藏精，主骨生髓，通脑”，即“补肾益脑”之说，前期研究显示巴戟天低聚糖具有改善痴呆大鼠学习记忆能力、对神经细胞具有保护作用等活性，为进一步揭示其作用机制，项目基于中医“脑疾”与AD两者关系的现代实质，结合其胆碱能水平异常、氧化应激反应、兴奋性毒性、相关基因及蛋白表达异常等共同的病理现象，采用D-半乳糖联合Aβ制备AD大鼠模型，运用中药药理学、分析化学以及分子生物学的技术，采用Morrish水迷宫、库仑阵列电化学和酶标法等方法考察行为学、神经递质水平、氧化应激水平、能量代谢水平、胆碱能水平等；采用RT-PCR，Western-blot检测Aβ、tau、SYP、BAX、NF-κB 65、Capase-3等相关基因和蛋白表达水平的影响，初步揭示巴戟寡糖保护神经系统的作用机制，为巴戟天“补肾益脑”功效提供理论依据，同时也为补肾中药作用于阿尔茨海默病方面的研究提供借鉴。

阿尔茨海默病（AD）是由多因素引起的原发性神经系统退行性疾病，同时也是一种非常复杂及严重的脑损害性疾病。目前对AD的机理及治疗已进行了大量的研究，但至今尚无成熟有效的方法和药物来防治该疾病。为此，根据中医“肾藏精，主骨生髓，通脑”的脏象理论，本项目选择传统补肾要药巴戟天为研究对象，结合阿尔茨海默病的学习记忆障碍、氧化应激水平异常、特异性神经递质缺陷、兴奋性氨基酸神经毒性、能量代谢异常、蛋白及基因水平表达异常等主要病理特征，探讨巴戟天中低聚糖类有效成分的现代神经系统保护作用，阐明其补肾益脑之作用机制。通过研究发现，巴戟天低聚糖对神经系统的保护作用可能与其改善脑内氧化应激水平、保护胆碱能系统、促进脑内能量代谢以及调节单胺类神经递质的代谢路径和相关蛋白的表达水平等作用有关。本研究结果可为巴戟天低聚糖补肾益脑作用的新药研发以及相关功能性保健品的开发奠定基础，也可为糖类有效成分抗AD作用的深入研究提供参考。