兰州大学机构库 >药学院
天麻及其有效物质对阿尔兹海默症模型小鼠的作用机制研究
Alternative TitleMechanism of action of Gastrodia elata and its active substances on Alzheimer's disease model mice
赵文斌
Thesis Advisor陈朋
2019-03-10
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Degree Discipline微生物与生化药学
Keyword天麻 天麻素 香兰素 天麻多糖 肠道微生物 阿尔兹海默症 肠-脑轴
Abstract天麻Gastrodia elata Blume (G. elata)是兰科植物中的一种腐生多年生草本植物,原产于中国,韩国和日本。传统中医利用天麻的干燥块茎治疗头晕,瘫痪和癫痫已有几个世纪。近年的研究表明天麻不仅具有增强记忆、改善大脑、预防衰老的功效,而且对老年性痴呆症有一定的疗效,其疗效在多个国家得到证实。天麻水提取物可以改善D-半乳糖诱导的小鼠记忆障碍,减少氧自由基,防止神经元损伤,并通过γ-氨基丁酸 (GABA)神经能系统表现出抗焦虑样作用,显著改善神经功能缺损。天麻及其主要生物活性成分天麻素等多种成分已被证明具有多种功能作用,包括认知增强,神经保护,抗抑郁和抗炎等,可显著改善阿尔兹海默症 (Alzheimer disease,AD)模型小鼠的学习记忆功能。AD是一种中枢神经系统的多方面神经退行性疾病,其特征在于进行性认知功能障碍。AD的主要病理标志是存在大量老年斑,脑区神经原纤维缠结和胆碱能功能障碍。据流行病学统计,该病已成为威胁老人健康的最严重疾患之一。在该病理情况下,草药植物及其生物活性化合物作为中枢神经系统疾病的新治疗方案备受关注。而关于肠道微生态与各种慢性病的研究近几年呈指数增长,肠道微生态对各种疾病发展的影响得到国际的普遍认可。大多数人类慢性病不仅和人基因组有关,还和基因-环境相互作用(如肠道微生物就是重要因素)有关。这使得传统的“单药物-靶点”药物发现方法不那么适用。目前越来越多的研究发现中药的作用靶点包括宿主及其共生微生物,这使得中药有望作为潜在的新药进入西方市场。研究发现肠道菌群与中枢神经系统的生理功能和疾病密切相关。肠道共生微生物菌群可通过多种直接或间接途径影响宿主大脑和行为,通过探索肠道微生物菌群在肠-脑轴信息交流中对脑功能及行为影响的具体机制,以期发现一些预防和治疗中枢神经系统疾病的微生态新疗法。综上所述,本课题利用三氯化铝和D-半乳糖联合诱导建立了AD小鼠模型,然后用天麻水煎液、天麻素、香兰素、天麻多糖对AD模型小鼠进行了灌胃治疗,灌胃治疗一个月后,用水迷宫进行了药效学的筛选,天麻水煎液、天麻素、香兰素、天麻多糖对AD模型组小鼠的学习记忆能力和空间探索能力均不同程度上得到了改善。之后通过蛋白免疫印迹和免疫组化对小鼠海马体中P-Tau蛋白的表达进行了定量分析,各给药组小鼠海马体中P-Tau蛋白的表达得到了不同程度的抑制。通过肠道微生物16S rRNA测序分析探讨了各组中肠道菌群的丰度变化,在天麻水煎液高剂量发现了约氏乳杆菌、罗伊氏乳杆菌、鼠乳杆菌三种益生菌,为预防和延缓阿尔茨海默病提供了全新的思路与方法。
Other AbstractGastrodia elata Blume (G. elata) is a saprophytic perennial herb of the orchid family, native to China, Korea and Japan. Traditional Chinese medicine has used dry tuber of G. elata to treat dizziness, convulsions and epilepsy for centuries. Recent studies have shown that G. elata not only has the effect of enhancing memory, improving the brain, preventing aging, but also has a certain effect on Alzheimer's disease, and its efficacy has been confirmed in many countries. G. elata extract can improve D-galactose-induced memory impairment in mice, reduce oxygen free radicals, prevent neuronal damage, and exhibit anxiolytic-like effects through the γ-aminobutyric acid (GABA) nervous system. It can significantly improve neurological deficits. Gastrodia and its main bioactive ingredients, Gastrodin have been shown multiple functional effects, including cognitive enhancement, neuroprotection, anti-depression and anti-inflammatory, which can significantly improve Alzheimer's disease (AD) model mice learn memory function.AD is a multifaceted neurodegenerative disease of the central nervous system characterized by progressive cognitive dysfunction. The main pathological hallmark of AD is the presence of a large number of senile plaques, neurofibrillary tangles and cholinergic dysfunction in the brain. According to epidemiological statistics, the disease has become one of the most serious diseases that threaten the health of the elderly. Under pathological conditions, the potential of herbal plants and their biologically active compounds as new treatments for central nervous system diseases has received much attention. The research on intestinal micro-ecology and various chronic diseases has grown exponentially in recent years, and the influence of intestinal micro-ecology on the development of various diseases has been widely recognized internationally. Most human chronic diseases are not only related to the human genome, but also to gene-environment interactions (eg, intestinal microbes are important factors). This makes traditional "single drug-target" drug discovery methods less suitable. At present, more and more studies have found that the targets of traditional Chinese medicines include the host and its symbiotic microorganisms, which makes it possible for Chinese medicine to enter the Western market as a potential new drug. The study found that the intestinal flora is closely related to the physiological functions and diseases of the central nervous system. Intestinal symbiotic microbial flora can affect host brain and behavior through a variety of direct or indirect ways, by exploring the specific mechanisms of intestinal microbial flora in the brain-brain axis information exchange on brain function and behavior, in order to find some prevention and a new micro-ecological treatment for central nervous system diseases.In summary, this study established a mouse model of AD induced by D-gal and AlCl3 peroxidation, and then used water extract of Rhizoma Gastrodiae (WERG), gastrodin, vanillin, and gastrodia elata polysaccharide (RGPS) to intervene in AD model mice. After treatment and intragastric intervention for one month, the pharmacodynamics were screened with water maze. WERG, gastrodin, vanillin and RGPS had different learning and memory abilities and spatial exploration ability in AD model group. The degree has been improved. The expression of P-Tau protein in hippocampus of mice was quantitatively analyzed by western blotting and immunohistochemistry. The expression of P-Tau protein in hippocampus of each group was inhibited to some extent. The abundance of intestinal flora in each group was investigated by 16S rRNA sequencing analysis of intestinal microbes. The high-dose of WERG found three probiotics of Lactobacillus johnsonii, Lactobacillus reuteri and Lactobacillus reuteri, which provided a new idea and method for preventing and delaying Alzheimer's disease.
Pages63
URL查看原文
Language中文
Document Type学位论文
Identifierhttp://ir.lzu.edu.cn/handle/262010/343876
Collection药学院
Affiliation药学院
Recommended Citation
GB/T 7714
赵文斌. 天麻及其有效物质对阿尔兹海默症模型小鼠的作用机制研究[D]. 兰州. 兰州大学,2019.
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