溃疡性结肠炎患者血清色氨酸及其代谢轮廓分析的研究

发布时间：2018-04-01 00:02

  本文选题：溃疡性结肠炎　切入点：炎症性肠病　出处：《河北北方学院》2014年硕士论文

【摘要】：溃疡性结肠炎(Ulcerative colitis, UC)是一种累及结肠和直肠的慢性炎症性疾病。长期的证据显示：UC是遗传易感人群对共生菌群过度或不足的肠道粘膜免疫反应的结果。迄今为止，，发病机制仍不明确，无特异性和敏感性强的诊断标志物，缺乏临床诊断金标准。该疾病目前的治疗目标为诱导并维持临床缓解及粘膜愈合，防治并发症，改善患者生存质量，但治疗效果不甚满意。因此，UC在发病机制、诊断和治疗方面成为研究热点问题。最近有证据表明氨基酸在保持肠道健康中发挥了重要生物学作用，其中代表性氨基酸——色氨酸(L-tryptophan,Trp)是人体必需氨基酸，其代谢与免疫相关，当Trp代谢发生改变时可能会导致消化功能紊乱，如炎症性肠病(inflammatory bowel disease,IBD)、肠易激综合征(irritable bowel syndrome, IBS)、乳糜泻、憩室炎。因此研究UC患者血清Trp及其代谢产物可能为解决UC的这些热点问题打开新的思路。 实验中，我们选取40个个体的血清样本，其中包括20个UC患者（活动期和缓解期）的血清和20个健康志愿者（Healthy volunteers,HVs）的血清。每个UC患者的诊断均基于临床表现、内镜检查、组织学检查及影像学检查综合情况。疾病分型依靠蒙特利尔分类法，活动性分型依靠改良的梅奥指数评估。利用LC-MS/MS的方法检测血清Trp及其主要代谢产物。用单因素方差分析比较UC活动期患者，UC缓解期患者以及HVs中血清Trp之间的差异，用t检验的方法比较UC患者和HVs中血清Trp及其主要代谢产物的差异。两种检测物之间的相关性利用Spearman相关性分析法分析。 血清Trp检测和分析结果显示：1.活动期UC患者血清Trp水平显著低于缓解期UC患者和HVs (P0.05)，缓解期UC患者组与HVs无明显差异；2.活动期UC患者血清Trp与ESR呈负相关(r=-0.520*, P=0.024)，活动期UC血清Trp与CRP呈负相关(r=-0.523*, P=0.016)；3.活动期UC患者经常规治疗进入缓解期后，血清Trp水平有所提高(P0.05)。 Trp代谢物检测和分析结果显示：UC活动期患者的血清Trp代谢轮廓与HVs相比，黄尿酸(XA)、3-羟基-2-氨基丙甲酸(HAA)、5-羟色胺、吲哚-3-乳酸(ILA)、吲哚-3-丙酸(IPA)明显减低。邻氨基苯甲酸（AA）、5-羟基-吲哚-3-乙酸(HIAA)明显升高。其中差异最明显的是黄尿酸。 本实验不仅对UC患者(包括活动期和缓解期)与健康志愿者(HVs)血清Trp进行了定量分析,探讨了血清Trp水平在UC疾病进展过程中可能的作用和临床意义。同时还利用了2011年，朱文涛教授改进的液相色谱串联质谱法（LC-MS/MS）定量检测了UC活动期患者与HVs血清Trp的关键代谢产物，这些关键代谢产物分别来自Trp代谢中的犬尿氨酸途径、5-羟色胺途径以及细菌分解途径。这也是目前为止在UC患者中最完整的血清Trp代谢轮廓分析。通过全面的分析比较UC活动期患者与HVs血清Trp代谢情况，我们1.发现了UC活动期患者与HVs血清Trp不同代谢途径中Trp代谢产物的差异，其中差异最明显的的代谢产物为黄尿酸，为今后的进一步研究奠定了基础；2.了解了UC活动期患者血清Trp整体的分解代谢情况及关键代谢产物在UC发病机制中可能发挥的作用，为更好的了解UC的发病机制，寻找特异性诊断标志物及靶向治疗方法提供了参考价值。
[Abstract]:UC is a chronic inflammatory disease involving colon and rectum . The long - term evidence suggests that UC is a diagnostic marker that is susceptible to excessive or undergrowth of symbiotic bacteria populations . So far , the pathogenesis , diagnosis and treatment of the disease is not very satisfactory . The recent evidence suggests that amino acids play an important biological role in the maintenance of intestinal health .

Serum Trp and its major metabolites were assessed by LC - MS / MS . The correlation between serum Trp and its major metabolites in patients with UC , UC remission and HVs was compared by using LC - MS / MS .

The serum Trp levels in patients with UC were significantly lower than those in remission stage UC and HVs ( P0.05 ) .
2 . There was a negative correlation between Trp and ESR in patients with active UC ( r = -0 . 520 * , P = 0 . 024 ) , and Trp in active phase was negatively correlated with CRP ( r = - 0.523 * , P = 0 . 016 ) ;
3 . Serum Trp level in patients with UC increased significantly after routine therapy ( P0.05 ) .

The results of Trp metabolite detection and analysis showed that the serum Trp metabolism profile of patients with UC was significantly lower than that of HVs . The serum Trp metabolic profile of patients with UC was significantly lower than that of HVs . The results showed that the serum Trp metabolic profile of patients with UC was significantly lower than that of HVs . The results showed that anthranlic acid ( AA ) , 5 - hydroxy - indole - 3 - acetic acid ( HIAA ) increased significantly . The most obvious difference was the uric acid .

The serum Trp metabolism of patients with UC and HVs was analyzed quantitatively by LC - MS / MS . The key metabolites of Trp in patients with UC and HVs were analyzed quantitatively by LC - MS / MS .
2 . It is useful to understand the metabolism of Trp in serum Trp in patients with UC and the possible role of key metabolites in the pathogenesis of UC , and provide reference value for better understanding of pathogenesis of UC , finding specific diagnostic markers and targeting therapy .

【学位授予单位】：河北北方学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R574.62

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1 努尔比亚·吾布力;库热西·玉努斯;买买提卡斯木·吾布力艾山;连静静;哈木拉提·吾甫尔;;大鼠溃疡性结肠炎的代谢组学研究[J];新疆医科大学学报;2010年06期

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