兰州大学机构库 >生命科学学院
益生菌对高尿酸血症小鼠血清尿酸水平的影响及机制
Alternative TitleEffect and Mechanism of Probiotics on Mouse with Hyperuricemia Serum Uric Acid Level
叶泽
Thesis Advisor刘璞
2019-02-28
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Degree Discipline发育生物学
Keyword高血尿酸 修复 肠道微生物
Abstract尿酸是人体嘌呤代谢的最终产物,大量高嘌呤食物的摄入、嘌呤的异常代谢,以及肾脏功能的下降都可能导致高血尿酸的发生。高尿酸血症会导致关节及周围组织中尿酸盐的积累,引起痛风及其它并发症,如慢性肾脏疾病、高血压以及心血管类疾病。现阶段尚缺乏有效的长期控制血尿酸的干预方法。外源的嘌呤类化合物部分在肠道内被分泌黄嘌呤脱氨酶的大肠杆菌代谢形成尿酸,然后被机体吸收;内源形成的尿酸有三分之二通过肾脏排出,剩余的三分之一则由肠道排出,其中部分排出的尿酸会通过转运蛋白被肠道重吸收,因此增加尿酸在肠道内的分解和排出是一种降低血尿酸的潜在可行途径。肠道菌群中的乳酸菌和假单胞杆菌具有分解尿酸能力,能将尿酸代谢成尿囊素和尿素,且肠道菌群的结构与尿酸代谢异常之间也存在密切的相关性。近年来国内外对痛风病人粪便微生物菌群的测序分析发现,痛风患者的肠道菌群结构与正常人相比发生了显著变化。为了增强肠道微生物的尿酸分解能力,本实验首先从西北地区发酵食品浆水中筛选获得了一株具有较强尿酸降解能力的发酵乳杆菌JL-3,属于可食用的益生菌属。本论文主要研究了发酵乳杆菌JL-3对高血尿酸模型小鼠的血尿酸浓度,尿酸的排出,以及对小鼠肠道菌群结构和功能的影响。依据文献报道的方法我们联合使用氧嗪酸钾和尿酸构建了高尿酸血症的模型小鼠,每天通过灌胃的方式给予1×108CFU以上的发酵乳杆菌JL-3,然后检测小鼠的血清、尿液和粪便中尿酸的浓度变化以及血清中与肾功能及炎症相关的生化指标,同时对小鼠粪便菌群16S rRNA进行Illumina Miseq测序。结果显示,发酵乳杆菌JL-3干预后模型小鼠血清和尿液中的尿酸显著下降,而粪便中的尿酸含量提高;对小鼠肝肾的炎症因子检测发现,JL-3显著降低了肝肾以及血清中的IL-1β浓度;高血尿酸小鼠的肠道菌群在拟杆菌门的比例显著上调,而厚壁菌门和变形菌门的比例下降,在JL-3干预后部分恢复了小鼠的肠道菌群结构。在单独给予小鼠氧嗪酸钾提高小鼠血清尿酸,并给予JL-3并不能降低小鼠血液中的尿酸浓度。实验结果说明,JL-3定植在小鼠肠道中并维护整个肠道菌群的结构稳定,提高肠道菌群降解尿酸的能力;JL-3对内源尿酸的生成没有显著的抑制作用,主要通过增加尿酸在肠道中的排泄来降低血尿酸浓度,同时降低由高血尿酸引起的一些炎症反应。本研究提示功能益生菌作为膳食补充剂具有一定降低血尿酸的作用,为血尿酸的长期控制提供了一个新思路。
Other AbstractUric acid is the final product of purine metabolism in human body. The hyperuricemia may take place for intake of a large number of high purine foods, abnormal metabolism of purine, and the declining of renal function. Hyperuricemia can lead to the accumulation of urates in joints and surrounding tissues, leading to gout and other complications, such as chronic kidney disease, hypertension, and cardiovascular disease. Currently, there is no effective intervention method for controlling uric acid in blood over a long period of time. Part of exogenous purine compounds is metabolized by xanthine deaminase, which is secreted in the intestinal tract by E.coli to form uric acid. Then the uric acid is absorbed by the body. Two-thirds of the endogenous uric acid is excreted through the kidneys, and the remaining one-third is excreted from the intestines. Some of the excreted uric acid will be reabsorbed by the intestinal tract through the transporter protein. Therefore, increasing the decomposition and excretion of uric acid in the intestinal tract is a potential feasible way to reduce blood uric acid. Intestinal bacterium Lactobacillus and Pseudomonas capable decomposition uric acid into allantoin and urea. And the structure of gut microbiota is closely correlated with uric acid metabolism. In recent years the sequencing analysis patients fecal microbes flora with gout found that the structure of patients gut microbiota is changed dramatically compared with normal in home and abroad. In order to enhance the capacity of gut microbiota uric acid decomposition, the survey found there is a kind of fermented food Jiangshui in the north-west, and it can significant lower incidence of gout with the frequency increase of eating Jiangshui, so this study first screened Lactobacillus fermentium JL-3 belongs to the edible probiotics has strong uric acid degradation ability from Jiangshui. This paper mainly studied the effect of Lactobacillus fermentium JL-3 on the serum uric acid concentration, the excretion of uric acid, and the structure and function of gut microbiota in hyperuricemia mouse model. We combined oteracil potassium and uric acid to build hyperuricemia mouse model based on the method from literature. We give mouse more than 108 cfu Lactobacillus fermentium JL-3 by lavage every day, then we detect the change of mice serum, urine and feces uric acid concentration and the serum biochemical indexes related to renal function and inflammation. We also detect the 16S rRNA of mice fecal flora by Illumina Miseq sequencing. The results showed that in model mouse the serum and urine uric acid decreased significantly after the intervention of Lactobacillus fermentium JL-3, while the uric acid content in feces increased. The detection of inflammatory cytokines in mouse liver and kidney showed that JL-3 significantly reduced the concentration of IL-1β in liver, kidney and serum. The proportion of gut microbiota in hyperuricemia mouse is significantly increased in Bacteroidetes, while the proportion of Firmicutes and Proteobacteria is decreased. After the intervention of JL-3, the mouse gut microbiota structure is partially restored. When mice were only given oteracil potassium to increased serum uric acid, JL-3 did not reduce the uric acid concentration in the blood of mice. The results showed that JL-3 was planted into the intestinal tract of mice and maintained the structure of entire intestinal flora. Then the ability of the intestinal flora to degrade uric acid is improved. JL-3 has no significant inhibitory effect on the generation of endogenous uric acid, and mainly reduces the concentration of uric acid in blood by increasing the excretion of uric acid in the intestinal tract, and meanwhile reduces some inflammatory reactions caused by hyperuricemia. This study suggests that functional probiotics can reduce serum uric acid on a certain extent as dietary supplements. And it provides a new idea to control serum uric acid for a long time.
Pages58
URL查看原文
Language中文
Document Type学位论文
Identifierhttp://ir.lzu.edu.cn/handle/262010/341961
Collection生命科学学院
Affiliation生命科学学院
Recommended Citation
GB/T 7714
叶泽. 益生菌对高尿酸血症小鼠血清尿酸水平的影响及机制[D]. 兰州. 兰州大学,2019.
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