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  本文選題：潰瘍性結(jié)腸炎　切入點：炎癥性腸病　出處：《河北北方學(xué)院》2014年碩士論文

【摘要】：潰瘍性結(jié)腸炎(Ulcerative colitis, UC)是一種累及結(jié)腸和直腸的慢性炎癥性疾病。長期的證據(jù)顯示：UC是遺傳易感人群對共生菌群過度或不足的腸道粘膜免疫反應(yīng)的結(jié)果。迄今為止，，發(fā)病機制仍不明確，無特異性和敏感性強的診斷標志物，缺乏臨床診斷金標準。該疾病目前的治療目標為誘導(dǎo)并維持臨床緩解及粘膜愈合，防治并發(fā)癥，改善患者生存質(zhì)量，但治療效果不甚滿意。因此，UC在發(fā)病機制、診斷和治療方面成為研究熱點問題。最近有證據(jù)表明氨基酸在保持腸道健康中發(fā)揮了重要生物學(xué)作用，其中代表性氨基酸——色氨酸(L-tryptophan,Trp)是人體必需氨基酸，其代謝與免疫相關(guān)，當Trp代謝發(fā)生改變時可能會導(dǎo)致消化功能紊亂，如炎癥性腸病(inflammatory bowel disease,IBD)、腸易激綜合征(irritable bowel syndrome, IBS)、乳糜瀉、憩室炎。因此研究UC患者血清Trp及其代謝產(chǎn)物可能為解決UC的這些熱點問題打開新的思路。 實驗中，我們選取40個個體的血清樣本，其中包括20個UC患者（活動期和緩解期）的血清和20個健康志愿者（Healthy volunteers,HVs）的血清。每個UC患者的診斷均基于臨床表現(xiàn)、內(nèi)鏡檢查、組織學(xué)檢查及影像學(xué)檢查綜合情況。疾病分型依靠蒙特利爾分類法，活動性分型依靠改良的梅奧指數(shù)評估。利用LC-MS/MS的方法檢測血清Trp及其主要代謝產(chǎn)物。用單因素方差分析比較UC活動期患者，UC緩解期患者以及HVs中血清Trp之間的差異，用t檢驗的方法比較UC患者和HVs中血清Trp及其主要代謝產(chǎn)物的差異。兩種檢測物之間的相關(guān)性利用Spearman相關(guān)性分析法分析。 血清Trp檢測和分析結(jié)果顯示：1.活動期UC患者血清Trp水平顯著低于緩解期UC患者和HVs (P0.05)，緩解期UC患者組與HVs無明顯差異；2.活動期UC患者血清Trp與ESR呈負相關(guān)(r=-0.520*, P=0.024)，活動期UC血清Trp與CRP呈負相關(guān)(r=-0.523*, P=0.016)；3.活動期UC患者經(jīng)常規(guī)治療進入緩解期后，血清Trp水平有所提高(P0.05)。 Trp代謝物檢測和分析結(jié)果顯示：UC活動期患者的血清Trp代謝輪廓與HVs相比，黃尿酸(XA)、3-羥基-2-氨基丙甲酸(HAA)、5-羥色胺、吲哚-3-乳酸(ILA)、吲哚-3-丙酸(IPA)明顯減低。鄰氨基苯甲酸（AA）、5-羥基-吲哚-3-乙酸(HIAA)明顯升高。其中差異最明顯的是黃尿酸。 本實驗不僅對UC患者(包括活動期和緩解期)與健康志愿者(HVs)血清Trp進行了定量分析,探討了血清Trp水平在UC疾病進展過程中可能的作用和臨床意義。同時還利用了2011年，朱文濤教授改進的液相色譜串聯(lián)質(zhì)譜法（LC-MS/MS）定量檢測了UC活動期患者與HVs血清Trp的關(guān)鍵代謝產(chǎn)物，這些關(guān)鍵代謝產(chǎn)物分別來自Trp代謝中的犬尿氨酸途徑、5-羥色胺途徑以及細菌分解途徑。這也是目前為止在UC患者中最完整的血清Trp代謝輪廓分析。通過全面的分析比較UC活動期患者與HVs血清Trp代謝情況，我們1.發(fā)現(xiàn)了UC活動期患者與HVs血清Trp不同代謝途徑中Trp代謝產(chǎn)物的差異，其中差異最明顯的的代謝產(chǎn)物為黃尿酸，為今后的進一步研究奠定了基礎(chǔ)；2.了解了UC活動期患者血清Trp整體的分解代謝情況及關(guān)鍵代謝產(chǎn)物在UC發(fā)病機制中可能發(fā)揮的作用，為更好的了解UC的發(fā)病機制，尋找特異性診斷標志物及靶向治療方法提供了參考價值。
[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 .

【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R574.62

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中國期刊全文數(shù)據(jù)庫 前1條

1 努爾比亞·吾布力;庫熱西·玉努斯;買買提卡斯木·吾布力艾山;連靜靜;哈木拉提·吾甫爾;;大鼠潰瘍性結(jié)腸炎的代謝組學(xué)研究[J];新疆醫(yī)科大學(xué)學(xué)報;2010年06期

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