不同影像学表型慢性阻塞性肺疾病患者吸入噻托溴铵治疗后的血清代谢标志物研究

发布时间：2018-04-14 11:32

本文选题：慢性阻塞性肺疾病 + 影像学分型　；参考：《昆明医科大学》2017年硕士论文

【摘要】：[目的]本研究采用基于核磁共振(Nuclear magnetic resonance,NMR)的代谢组学研究方法,比较E型慢性阻塞性肺疾病(Chronic obstructive pulmonary disease,COPD)、M型COPD吸入噻托溴铵治疗3月前、后及与正常对照组的血清代谢谱,筛选血清代谢标志物并探讨其临床应用价值。[方法]选择昆明医科大学第一附属医院住院部及门诊2015年10月至2016年10月符合试验要求的E型COPD患者(10例)、M型COPD患者(10例)及体检中心正常健康人(10例),收集E型、M型稳定期COPD治疗前、后及正常对照组空腹血清标本,应用1H-NMR技术对各组血清标本进行代谢组学分析。将原始数据导入SIMCA-P+软件进行分析,采用主成分分析(principal component analysis,PCA)和偏最小二乘判别分析(Partial Least Square Discriminant Analysis,PLS-DA)进行建模,通过变量权重值(variable importance for projection,VIP)分析,初步筛选对组间差异贡献最大(VIP1.0)的化学位移。进一步应用对筛选出的化学位移进行单变量分析,最终筛选出差异倍数大于2且差异具有统计学意义(P0.05)的化学位移,结合国内外研究,代谢谱峰指认识别软件(chenomx NMR suite software)对代谢物进行指认,得到符合要求的代谢标志物。[结果]1..E型COPD吸入噻托溴铵治疗前、后组分别与正常对照组血清代谢物对比:模式识别分析所建立模型能将两组显著区分。E型COPD患者吸入噻托溴铵治疗前组与正常对照组血清代谢物对比检出18种代谢物,E型COPD患者吸入噻托溴铵治疗后组与正常对照组血清代谢物对比检出12种代谢物。鸟氨酸、L-脯氨酸、2-羟基异丁酸酯、乳酸、脂质在吸入噻托溴铵治疗前降低,治疗后升高;而脂蛋白、苯丙氨酸、色氨酸在治疗前浓度升高,治疗后浓度降低,其他无变化。2.M型COPD吸入噻托溴铵治疗前、后组分别与正常对照组血清代谢物对比:模式识别分析所建立模型能将两组显著区分。M型COPD患者吸入噻托溴铵治疗前组与正常对照组血清代谢物对比检出21种代谢物,M型COPD患者吸入噻托溴铵治疗后组与正常对照组血清代谢物对比检出18种代谢物。D-葡萄糖在吸入噻托溴铵治疗前降低,治疗后升高;而L-缬氨酸在治疗前浓度升高,治疗后浓度降低,其他无变化。3.E型COPD患者治疗后与治疗前血清代谢物对比:模式识别分析所建立模型能将两组显著区分。检出9种代谢物,其中L-丙氨酸、甘氨酸、苯丙氨酸、酪氨酸、柠檬酸、乳酸、吡哆醇琥珀酸浓度在治疗后组降低,胆碱、吡哆醇浓度升高。4.M型COPD患者治疗后组与治疗前组血清代谢物对比:模式识别分析所建立模型能将两组显著区分。检出4种代谢物,其中色氨酸、肌苷酸、丙酮浓度在M型COPD治疗后组降低,鸟氨酸浓度升高。[结论]通过基于核磁共振的代谢组学研究方法,利用代谢谱所建立的模型可较好区分E型、M型COPD患者与正常对照组,E型COPD患者吸入噻托溴铵治疗前、后组,M型COPD组患者治疗前、后组血清代谢普。不同影像学分型的COPD患者血清代谢谱在治疗前、后存在显著差异,且两组存在特异性变化的代谢物在治疗后均有向正常人靠拢趋势,但噻托溴铵对E型COPD患者的代谢效果更明显,检测相关代谢物浓度有望实现COPD个体化治疗。
[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.

【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R563.9

【参考文献】