溃疡性结肠炎氨基酸代谢轮廓分析及其临床意义研究

发布时间：2018-03-31 17:07

本文选题：溃疡性结肠炎　切入点：高效液相色谱-质谱联用技术　出处：《山西医科大学》2014年硕士论文

【摘要】：目的溃疡性结肠炎（Ulcerative colitis, UC）是一种病因尚不十分清楚的直肠和结肠慢性非特异性炎症性疾病，其病因和发病机制尚未完全明确，临床缺乏诊断的金标准，治疗目标主要是诱导并维持临床缓解及黏膜愈合，防止并发症，改善患者生存质量。国外研究显示溃疡性结肠炎伴有氨基酸含量的改变，为明确氨基酸与溃疡性结肠炎之间的联系，通过高效液相色谱-质谱联用技术（HPLC-MS/MS）稳定同位素内标法对溃疡性结肠炎血清、尿液中氨基酸代谢轮廓分析，探讨氨基酸含量的变化与溃疡性结肠炎之间的关系，进一步明确UC病因及发病机制，寻找生物标志物，用于早期诊断及指导治疗等。方法收集2012年10月至2013年11月间收住解放军第309医院的44例溃疡性结肠炎（UC）患者的血清及尿液样品作为试验组，对照组选用25例正常体检者的血清及尿液样品。所有样品给予实验前处理，内标和标准溶液配制，加入标准溶液于样品中，采用高效液相色谱-质谱联用技术检测，进行数据处理及统计分析。结果通过对UC患者血清氨基酸的代谢轮廓分析，与对照组相比，血清中谷氨酸、谷氨酰胺、甲硫氨酸、色氨酸和组氨酸的浓度水平发生了明显的下调（P＜0.05），天冬酰胺和异亮氨酸的浓度水平发生了明显的上调（P＜0.05），差异有统计学意义；经过临床干预治疗后，除异亮氨酸外，余氨基酸浓度变化都趋向于正常趋势，但差异无统计学意义（P＞0.05）。通过对UC患者尿液氨基酸的代谢轮廓分析，与对照组相比，尿液中脯氨酸、甲硫氨酸、缬氨酸和谷氨酰胺的浓度水平发生了明显下调（P＜0.05），甘氨酸、丝氨酸和组氨酸浓度水平发生了明显上调（P＜0.05），差异有统计学意义；经过临床干预治疗后，除甲硫氨酸和缬氨酸外，余氨基酸浓度变化都趋向于正常趋势，但差异无统计学意义（P＞0.05）。结论UC患者中谷氨酸、谷氨酰胺、甲硫氨酸、色氨酸、组氨酸、天冬酰胺、异亮氨酸、脯氨酸、缬氨酸、甘氨酸和丝氨酸的浓度水平与对照组相比存在明显的差异（P＜0.05），差异有统计学意义，提示着溃疡性结肠炎存在着氨基酸代谢的变化，研究说明这些氨基酸与UC的发病机制及其发病过程存在着一定的关系，为溃疡性结肠炎的发病机制提供新的见解，氨基酸可作为潜在的诊断生物标志物，用于UC疾病的早期诊断以及指导治疗、预防复发等。
[Abstract]:Objective Ulcerative colitis (UCC) is a chronic nonspecific inflammatory disease of the rectum and colon, which is still unknown in etiology. The etiology and pathogenesis of UCis are not completely clear, and there is no gold standard for clinical diagnosis. The main goal of treatment is to induce and maintain clinical remission and mucosal healing, to prevent complications, and to improve the quality of life of patients. Foreign studies have shown that ulcerative colitis is accompanied by changes in amino acid content. In order to clarify the relationship between amino acids and ulcerative colitis, the metabolic profiles of amino acids in serum and urine of ulcerative colitis were analyzed by HPLC-MS / MS stable isotope internal standard method. To explore the relationship between the change of amino acid content and ulcerative colitis, to further clarify the etiology and pathogenesis of UC, and to search for biomarkers. Methods Serum and urine samples of 44 patients with ulcerative colitis (UCC) admitted to the 309 Hospital of PLA between October 2012 and November 2013 were collected for early diagnosis and treatment. In the control group, serum and urine samples were collected from 25 normal persons. All the samples were pretreated, prepared with internal standard and standard solution, added to the sample, and detected by high performance liquid chromatography-mass spectrometry (HPLC / MS). Results compared with the control group, the levels of glutamate, glutamine, methionine in the serum of UC patients were compared with those in the control group. The concentrations of tryptophan and histidine decreased significantly (P < 0.05), and the concentrations of asparagine and isoleucine increased significantly (P < 0.05). The change of residual amino acid concentration tended to the normal trend, but the difference was not statistically significant (P > 0.05). Compared with the control group, the concentrations of proline, methionine, valine and glutamine in the urine of UC patients were significantly down-regulated (P < 0.05) and glycine, compared with the control group, the levels of proline, methionine, valine and glutamine were significantly down-regulated (P < 0.05). The concentration of serine and histidine increased significantly (P < 0.05), and after clinical intervention, the concentration of residual amino acids tended to change to a normal trend, except for methionine and valine. Conclusion the levels of glutamate, glutamine, methionine, tryptophan, histidine, asparagine, isoleucine, proline, valine in UC patients were not significantly different (P > 0.05). The concentrations of glycine and serine were significantly different from those of the control group (P < 0.05), which indicated that there was a change in amino acid metabolism in ulcerative colitis. The study shows that these amino acids have some relationship with the pathogenesis and pathogenesis of UC, and provide new insights into the pathogenesis of ulcerative colitis. Amino acids can be used as potential biomarkers for diagnosis of ulcerative colitis. It can be used for early diagnosis and treatment of UC disease, prevention of recurrence and so on.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R574.62

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