尿毒症毒素作为诱发性危险或稳态相关分子模式的研究

发布时间：2018-06-21 03:55

本文选题：尿毒症毒素 + 危险信号相关分子模式　；参考：《山西医科大学》2017年硕士论文

【摘要】：目的:研究某些内源性代谢产物在慢性肾脏病患者体内浓度升高的机制,以及这些内源性代谢产物是否可以激活危险信号相关分子模式受体,诱导炎症发生,并进一步分析这些内源性代谢产物的调控机制。方法:在代谢产物以及基因数据库中,找到尿毒症毒素受体及其关键合成酶与转化酶的编码基因。在NIH-Geo数据库中找到代谢性疾病及炎症通路相关的13个微阵列数据库,使用GEO2R的分析方法分析尿毒症毒素相关基因,选择p?0.05的基因分析结果。结果:在慢性肾脏病中,小分子尿毒症毒素种类占人体小分子代谢产物的1/80;尿毒症毒素浓度不只在慢性肾脏病中升高,在其他疾病中也会升高;蛋白结合型尿毒症毒素可以促进或抑制炎症因子的表达;与代谢综合征和2型糖尿病患者相比,慢性肾脏病患者肾小管及心血管疾病患者脂肪组织中尿毒症毒素基因显著升高;caspase-1通路和TNF-alpha通路明显上调尿毒症毒素基因表达;调节性T细胞显著下调尿毒症毒素基因的表达。游离性尿毒症毒素中,20%促进炎症反应,12%抑制炎症反应;蛋白结合型尿毒症毒素中,14%促进炎症反应,5%抑制炎症反应;在尿毒症相关代谢性疾病中,19.52%尿毒症毒素相关基因表达上调,33.14%尿毒症毒素相关基因表达下调。结论:尿毒症毒素由于肾脏滤过功能衰竭而被动积累,并且在慢性肾脏病中选择性浓度升高。尿毒症毒素可以作为危险或稳态相关分子模式调控炎症反应,其调控途径为包括caspase-1通路在内的炎症因子通路。
[Abstract]:Aim: to investigate the mechanism of elevated concentrations of some endogenous metabolites in patients with chronic kidney disease and whether these endogenous metabolites can activate risk signal-related molecular model receptors and induce inflammation. The regulation mechanism of these endogenous metabolites was further analyzed. Methods: the genes encoding uremic toxin receptors and their key synthase and invertase were found in metabolites and gene databases. Thirteen microarray databases related to metabolic diseases and inflammatory pathways were found in NIH-Geo database. The analysis method of GEO2R was used to analyze uremic toxin-related genes, and the results of p0.05 gene analysis were selected. Results: in chronic kidney disease, the type of small molecule uremic toxin accounted for 1 / 80 of human small molecule metabolites, the concentration of uremic toxin increased not only in chronic kidney disease, but also in other diseases. Protein-binding uremic toxins can promote or inhibit the expression of inflammatory factors in patients with metabolic syndrome and type 2 diabetes. Uremic toxin gene increased significantly in renal tubules and adipose tissue of patients with chronic kidney disease and TNF-alpha pathway upregulated the expression of uremic toxin gene, and regulatory T cells significantly down-regulated the expression of uremic toxin gene. 20% of free uremic toxins promoted the inflammatory response and 12% inhibited the inflammatory response, while 14% of the protein-binding uremic toxins promoted the inflammatory response and 5% of the protein-binding uremic toxins inhibited the inflammatory response. In uremic related metabolic diseases, 19.52% of uremic toxin-associated genes were up-regulated and 33.14% of uremic toxin-associated genes were down-regulated. Conclusion: uremic toxin accumulates passively because of renal filtration failure, and the selective concentration in chronic kidney disease is increased. Uremic toxin can be used as a dangerous or homeostasis related molecular model to regulate inflammatory response, and its regulatory pathway is the inflammatory factor pathway, including the caspase-1 pathway.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692.5

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