發(fā)布時間：2018-06-13 06:43

  本文選題：AKK亞型 + 精神疾病　； 參考：《南方醫(yī)科大學(xué)》2017年碩士論文

【摘要】：肥胖及糖尿病嚴(yán)重威脅著人類健康,它們也能顯著增加神經(jīng)精神類疾病的發(fā)病率,如抑郁癥、癡呆、中風(fēng)及記憶力衰退等。全身慢性系統(tǒng)性炎癥是肥胖及糖尿病患者的共同特征,這樣的慢性炎癥也出現(xiàn)在中樞神經(jīng)系統(tǒng)內(nèi),它是連接肥胖、糖尿病和神經(jīng)精神疾病的重要紐帶。Akkermansia muciniphila(簡稱為AKK)2004年被首次分離培養(yǎng)。研究發(fā)現(xiàn)AKK與肥胖及2型糖尿病密切相關(guān),在2型糖尿病患者中,AKK的數(shù)量顯著顯著下降。此外,動物研究發(fā)現(xiàn),給予AKK灌胃能顯著改善由高脂飲食誘導(dǎo)的代謝紊亂,包括像脂肪堆積,內(nèi)毒素血癥,肥胖病及胰島素抵抗等.最新的研究發(fā)現(xiàn),同一種的細(xì)菌不同菌株對體內(nèi)免疫細(xì)胞的作用不一定是相同或相似的,也存在一些剛好“相左”的作用。即雖然它們結(jié)構(gòu)相似,卻并不完全起到協(xié)同作用,也存在相互制衡。本團(tuán)隊從臨床糞便樣本中分離出一株AKK,并經(jīng)過測序分析確認(rèn)其是與模式菌株不同的亞型(簡稱為AKK亞型)。1研究目的:1.1確認(rèn)該AKK亞型的減緩體重增加和改善血糖控制的功能及探索其作用機(jī)制。1.2探索該AKK亞型能否預(yù)防肥胖相關(guān)精神疾病的出現(xiàn)及其作用的機(jī)制。2方法2.1 40只8周齡SPF級雌性C57BL/6小鼠隨機(jī)分為四組,分別為高脂飲食灌胃組,高脂飲食對照組,正常飲食灌胃組,正常飲食對照組。灌胃組每天每只小鼠按2×108CFU/0.2ml劑量給予AKK亞型灌胃,對照組給予相同體積的PBS灌胃。每周測量小鼠體重及飼料消耗量,實驗持續(xù)10個月。2.2實驗中期及結(jié)束時測定小鼠的空腹血糖,進(jìn)行口服糖耐量實驗2.3實驗前及實驗后測定糞便中AKK的定植量2.4實驗結(jié)束時進(jìn)行糖水偏愛實驗和Y迷宮實驗,分析小鼠的抑郁及空間記憶情況。2.5腸道菌群宏基因組學(xué)測序2.6血清中炎癥及腦功能相關(guān)指標(biāo)檢測2.7體外測定AKK亞型及模式菌株產(chǎn)生短鏈脂肪酸2.8病理學(xué)觀察2.9統(tǒng)計學(xué)分析3結(jié)果3.1 AKK亞型能顯著減少高脂飲食及正常飲食小鼠的飼料消耗量,顯著減輕高脂飲食小鼠的體重。3.2灌胃前各組小鼠AKK的定植量沒有顯著差異,灌胃后,灌胃組的定植量顯著高于對照組。3.3 AKK亞型能降低高脂飲食小鼠的空腹血糖及提高糖耐受能力。3.4糖水偏愛:高脂飲食小鼠的糖水消耗率均顯著低于正常飲食小鼠;AKK亞型灌胃不能改善小鼠抑郁情況;Y迷宮實驗:AKK亞型灌胃顯著改善高脂飲食小鼠的空間記憶力。3.5正常灌胃組IL-10濃度顯著高于另外三組,高脂灌胃組的IL-10也略高于另外兩組;高脂對照組色氨酸顯著高于另外三組,另外三組的色氨酸濃度沒有顯著差異;高脂飲食小鼠的五羥色胺濃度均顯著低于正常飲食小鼠。3.6飲食因素能顯著改變腸道菌群結(jié)構(gòu),高脂飲食顯著降低腸道菌群多樣性,并導(dǎo)致雙歧桿菌數(shù)量下降,擬桿菌及嗜膽菌屬數(shù)量上升;AKK亞型能顯著增加雙歧桿菌屬,降低嗜膽菌屬,并與擬桿菌成負(fù)相關(guān)關(guān)系。3.7 AKK亞型能增加高脂飲食小鼠腸道中的杯狀細(xì)胞的數(shù)量并能減輕肝臟脂肪變性。3.8 AKK亞型能產(chǎn)生比模式菌株更高濃度的乙酸、丙酸和異戊酸。4結(jié)論4.1 AKK亞型能顯著減緩高脂飲食小鼠體重增加,并改善血糖控制4.2 AKK亞型能改善由于高脂飲食誘導(dǎo)的記憶力衰退4.3 AKK亞型可能通過提高腸道中雙歧桿菌,降低嗜膽菌屬及擬桿菌,產(chǎn)生短鏈脂肪酸及降低機(jī)體炎癥水平對宿主發(fā)揮作用
[Abstract]:Obesity and diabetes are a serious threat to human health. They can also significantly increase the incidence of neuropsychiatric disorders, such as depression, dementia, stroke, and memory decline. Systemic chronic systemic inflammation is a common feature of obesity and diabetes. This chronic inflammation is also found in the central nervous system, which is linked to obesity and sugar. .Akkermansia muciniphila (AKK), an important link between urinary and neuropsychiatric disorders, was first isolated in 2004. The study found that AKK is closely related to obesity and type 2 diabetes. In type 2 diabetic patients, the number of AKK is significantly decreased. In addition, animal studies have found that giving AKK to the stomach can significantly improve the induction of high fat diet. Metabolic disorders, including fat accumulation, endotoxemia, obesity and insulin resistance. Recent studies have found that different strains of the same bacteria do not have the same or similar effects on immune cells in the body, and there are some just "left" effects. The team isolated a AKK from the clinical stool sample and sequenced it to confirm that it was a subtype (AKK subtype) that was different from the model strain (referred to as AKK subtype).1 research purposes: 1.1 confirm the AKK subtype's weight loss increase and improve the function of blood glucose control and explore its mechanism of action.1.2 to explore whether the AKK subtype is possible The mechanism of prevention of obesity related mental illness and its mechanism.2 method 2.140 8 weeks old SPF female C57BL/6 mice were randomly divided into four groups: high fat diet gavage group, high fat diet control group, normal diet gavage group, normal diet control group. Each mice in the gavage group were given the AKK subtype of AKK subtype every day at 2 x 108CFU/0.2ml doses per mouse. The control group was given the same volume of PBS gavage. The weight and feed consumption of mice were measured every week. The experiment lasted 10 months at the mid-term and the end of the.2.2 experiment. The experiment was carried out before and after the oral glucose tolerance test (2.3), and the fixed amount of AKK in the feces was measured at the end of the experiment of sugar water preference and the Y labyrinth experiment. Analysis of depression and spatial memory in mice.2.5 intestinal microflora sequencing 2.6 serum inflammation and brain function related indicators detection 2.7 in vitro determination of AKK subtype and pattern strain producing short chain fatty acid 2.8 pathological observation 2.9 statistical analysis 3 Results 3.1 AKK subtype can significantly reduce the diet of high fat diet and normal diet mice feeding There was no significant difference in the amount of AKK in the mice before gavage of high fat diet (.3.2). After gavage, the colonization of the gavage group was significantly higher than that of the control group.3.3 AKK subtype, which could reduce the fasting blood glucose of the high fat diet mice and improve the sugar tolerance.3.4 sugar water preference: the sugar water consumption rate of the high fat diet mice were all Significantly lower than normal diet mice, AKK subtype of gastric perfusion could not improve the depression of mice; Y labyrinth experiment: AKK subtype of gastric perfusion significantly improved the spatial memory of high fat diet mice, IL-10 concentration in the normal gavage group was significantly higher than the other three groups, and the IL-10 in the high fat gavage group was slightly higher than the other two groups, and the high fat control group was significantly higher than that of the other group. In the three group, there was no significant difference in the concentration of tryptophan in the other three groups; the concentration of five HT in the high fat diet mice was significantly lower than the.3.6 diet in the normal diet mice. The high fat diet significantly reduced the diversity of the intestinal flora, and the number of bifidobacteria, and the increase in the number of Bacillus and eosinophilia; AKK The subtype can significantly increase the genus Bifidobacterium and lower the genus pheophilia, and the.3.7 AKK subtype can increase the number of goblet cells in the intestinal tract of the high fat diet mice and reduce the liver fatty degeneration.3.8 AKK subtype to produce a higher concentration of acetic acid than the model strain. The 4.1 AKK subtype of propionic acid and isovalerate.4 can be found to be significant. The increase in weight of the high fat diet mice and the improvement of the 4.2 AKK subtype of blood glucose control can improve the memory decline induced by the high fat diet 4.3 AKK subtypes by raising the Bifidobacterium in the intestinal tract, reducing the phinophilia and bacteriobacteria, producing short chain fatty acids and reducing the level of inflammatory disease to the host.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R741;R58

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Rahul Shubhra Mandal;Sudipto Saha;Santasabuj Das;;Metagenomic Surveys of Gut Microbiota[J];Genomics,Proteomics & Bioinformatics;2015年03期

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本文編號：2013097