本文選題：慢性阻塞性肺疾病 + 影像學(xué)分型��； 參考：《昆明醫(yī)科大學(xué)》2017年碩士論文

【摘要】：[目的]本研究采用基于核磁共振(Nuclear magnetic resonance,NMR)的代謝組學(xué)研究方法,比較E型慢性阻塞性肺疾病(Chronic obstructive pulmonary disease,COPD)、M型COPD吸入噻托溴銨治療3月前、后及與正常對(duì)照組的血清代謝譜,篩選血清代謝標(biāo)志物并探討其臨床應(yīng)用價(jià)值。[方法]選擇昆明醫(yī)科大學(xué)第一附屬醫(yī)院住院部及門診2015年10月至2016年10月符合試驗(yàn)要求的E型COPD患者(10例)、M型COPD患者(10例)及體檢中心正常健康人(10例),收集E型、M型穩(wěn)定期COPD治療前、后及正常對(duì)照組空腹血清標(biāo)本,應(yīng)用1H-NMR技術(shù)對(duì)各組血清標(biāo)本進(jìn)行代謝組學(xué)分析。將原始數(shù)據(jù)導(dǎo)入SIMCA-P+軟件進(jìn)行分析,采用主成分分析(principal component analysis,PCA)和偏最小二乘判別分析(Partial Least Square Discriminant Analysis,PLS-DA)進(jìn)行建模,通過變量權(quán)重值(variable importance for projection,VIP)分析,初步篩選對(duì)組間差異貢獻(xiàn)最大(VIP1.0)的化學(xué)位移。進(jìn)一步應(yīng)用對(duì)篩選出的化學(xué)位移進(jìn)行單變量分析,最終篩選出差異倍數(shù)大于2且差異具有統(tǒng)計(jì)學(xué)意義(P0.05)的化學(xué)位移,結(jié)合國(guó)內(nèi)外研究,代謝譜峰指認(rèn)識(shí)別軟件(chenomx NMR suite software)對(duì)代謝物進(jìn)行指認(rèn),得到符合要求的代謝標(biāo)志物。[結(jié)果]1..E型COPD吸入噻托溴銨治療前、后組分別與正常對(duì)照組血清代謝物對(duì)比:模式識(shí)別分析所建立模型能將兩組顯著區(qū)分。E型COPD患者吸入噻托溴銨治療前組與正常對(duì)照組血清代謝物對(duì)比檢出18種代謝物,E型COPD患者吸入噻托溴銨治療后組與正常對(duì)照組血清代謝物對(duì)比檢出12種代謝物。鳥氨酸、L-脯氨酸、2-羥基異丁酸酯、乳酸、脂質(zhì)在吸入噻托溴銨治療前降低,治療后升高;而脂蛋白、苯丙氨酸、色氨酸在治療前濃度升高,治療后濃度降低,其他無變化。2.M型COPD吸入噻托溴銨治療前、后組分別與正常對(duì)照組血清代謝物對(duì)比:模式識(shí)別分析所建立模型能將兩組顯著區(qū)分。M型COPD患者吸入噻托溴銨治療前組與正常對(duì)照組血清代謝物對(duì)比檢出21種代謝物,M型COPD患者吸入噻托溴銨治療后組與正常對(duì)照組血清代謝物對(duì)比檢出18種代謝物。D-葡萄糖在吸入噻托溴銨治療前降低,治療后升高;而L-纈氨酸在治療前濃度升高,治療后濃度降低,其他無變化。3.E型COPD患者治療后與治療前血清代謝物對(duì)比:模式識(shí)別分析所建立模型能將兩組顯著區(qū)分。檢出9種代謝物,其中L-丙氨酸、甘氨酸、苯丙氨酸、酪氨酸、檸檬酸、乳酸、吡哆醇琥珀酸濃度在治療后組降低,膽堿、吡哆醇濃度升高。4.M型COPD患者治療后組與治療前組血清代謝物對(duì)比:模式識(shí)別分析所建立模型能將兩組顯著區(qū)分。檢出4種代謝物,其中色氨酸、肌苷酸、丙酮濃度在M型COPD治療后組降低,鳥氨酸濃度升高。[結(jié)論]通過基于核磁共振的代謝組學(xué)研究方法,利用代謝譜所建立的模型可較好區(qū)分E型、M型COPD患者與正常對(duì)照組,E型COPD患者吸入噻托溴銨治療前、后組,M型COPD組患者治療前、后組血清代謝普。不同影像學(xué)分型的COPD患者血清代謝譜在治療前、后存在顯著差異,且兩組存在特異性變化的代謝物在治療后均有向正常人靠攏趨勢(shì),但噻托溴銨對(duì)E型COPD患者的代謝效果更明顯,檢測(cè)相關(guān)代謝物濃度有望實(shí)現(xiàn)COPD個(gè)體化治療。
[Abstract]:[Objective] this study was based on nuclear magnetic resonance (Nuclear magnetic resonance, NMR) the metabonomics research method, comparison of E type of chronic obstructive pulmonary disease (Chronic obstructive pulmonary disease, COPD, M) COPD tiotropium bromide inhalation therapy in March before and after the serum metabolism and the normal control group spectrum, screening and to explore its clinical value. Methods selection of inpatient and outpatient from October 2015 to October 2016 to meet the test requirements of E type COPD patients in the First Affiliated Hospital of Kunming Medical University marker serum metabolism (10 cases), patients with M type COPD (10 cases) and examination center of normal healthy people (10 cases) were collected, E type, M type stability after the period of COPD before treatment, and the normal control group, fasting serum sample, the application of 1H-NMR technology on serum samples were studied using metabonomics analysis. The original data into SIMCA-P+ software analysis, using principal component analysis (principal component Analysis, PCA) and partial least squares discriminant analysis (Partial Least Square Discriminant Analysis, PLS-DA) are modeled by variable weight value (variable importance for projection, VIP) analysis, preliminary screening contributed to the differences between the groups (VIP1.0). The chemical shifts of the further application of single variable analysis of chemical shifts were screened, finally selected fold difference is greater than 2 and the difference was statistically significant (P0.05) chemical shift, combined with domestic and foreign research, identify the metabolic Pufeng recognition software (chenomx NMR suite software) for identification of metabolites, are obtained to meet the requirements of metabolic markers. Results]1..E COPD inhalation of tiotropium bromide before treatment, after the group respectively the normal control group, plasma metabolites in contrast: pattern recognition analysis model can significantly distinguish two groups before treatment of tiotropium bromide inhalation tiotropium group and normal control.E COPD patients Group comparison of plasma metabolites were detected in 18 metabolites, E inhalation tiotropium COPD patients tiotropium bromide treatment group and normal control group comparison of plasma metabolites were detected in 12. L- metabolites ornithine, proline, 2- hydroxy isobutyric acid ester, lactic acid, lipid in tiotropium reduced before treatment, after treatment.; lipoprotein, phenylalanine, tryptophan before treatment concentration increased, the concentration decreased after treatment, no other changes of.2.M type COPD tiotropium bromide inhalation before treatment group and normal control group respectively after blood metabolites in contrast: pattern recognition analysis model can significantly distinguish two groups of tiotropium bromide treatment the former group and normal control group comparison of plasma metabolites were detected in 21 patients with COPD type.M metabolites inhalation tiotropium inhalation in patients with COPD type M, thiophene tiotropium bromide treatment group and normal control group comparison of plasma metabolites were detected in 18.D- glucose metabolites in tiotropium bromide inhalation treatment Before treatment decreased after treatment increased L- before treatment; valine concentration, concentration decreased after treatment, no other changes in.3.E type COPD patients before and after treatment, blood metabolites in contrast: pattern recognition analysis model can significantly distinguish two groups. There were 9 metabolites, including L- alanine, glycine. Phenylalanine, tyrosine, citric acid, lactic acid, succinic acid, pyridoxine concentration in the treatment group decreased, choline, pyridoxine concentration in the treatment of COPD type.4.M group before treatment group serum metabolite contrast: pattern recognition analysis model can significantly distinguish two groups. There were 4 metabolites, including tryptophan, inosinic acid. The concentration of acetone group decreased at M COPD after treatment. Conclusion ornithine concentration increased by metabolic NMR study method based on spectrum established by metabolic model can distinguish patients with type E, type M and COPD The normal control group, E type COPD with tiotropium bromide inhalation before treatment, after treatment group, COPD group of patients with type M blood group before and after the Qing Dynasty Shepard. Serum metabolism in COPD patients with different classification of the spectrum before treatment, there was significant difference after two groups, and there were specific changes in metabolites after the treatment to the normal closing tendency, but the tiotropium metabolic effect of E type COPD were more obvious, related metabolite concentration detection is expected to achieve COPD individualized treatment.

【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R563.9

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本文編號(hào)：1749148