本文選題：結(jié)核性腦膜炎 + 超高效液相色譜�。� 參考：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:探尋結(jié)核性腦膜炎(Tuberculous meningitis,TBM)患者腦脊液和血清中的特異性代謝物質(zhì),通過分析研究這些代謝物質(zhì)在患者體內(nèi)數(shù)量和性質(zhì)的改變,以及其在疾病衍變過程中的代謝機(jī)制,尋找有代表性的代謝離子,輔助臨床對(duì)結(jié)核性腦膜炎的早期診斷,病情監(jiān)測,以改善患者預(yù)后。方法:采用超高效液相色譜與質(zhì)譜聯(lián)用(UPLC-MS)代謝組學(xué)技術(shù)平臺(tái)共分析腦脊液標(biāo)本47例,血清標(biāo)本107例。樣本來自取2014年11月-2016年12月在天津市海河醫(yī)院腦系科和結(jié)核科住院患者的腦脊液標(biāo)本共47例,其中TBM的患者21例,非結(jié)核性腦膜炎患者26例,另選取健康體檢者30例。最終研究對(duì)象共有102例,其中男57例,女45例;將其分成:結(jié)核性腦膜炎組患者21例,男/女為12/9,平均年齡(48.01±12.35)歲。對(duì)照組包括非結(jié)核性腦膜炎組(N-TBM組)26例,肺結(jié)核組(TB組)25例,健康對(duì)照組(N組)30例。其中N-TBM組男/女為14/12,平均年齡(45.56±19.43)歲,包括細(xì)菌性腦膜炎7例;病毒性腦膜炎15例,其它原因引起的腦膜炎4例;TB組25例,其中男15例,女10例,平均年齡(46.56±15.43)歲;健康對(duì)照組共30例,其中男16例,女14例,平均年齡(43.56±21.43)歲。腦脊液和血清樣品檢測均采用UPLC-MS。初步數(shù)據(jù)處理采用Mzmine2.0軟件;初步處理后的數(shù)據(jù)錄入SIMCA-P+12.0.1.0軟件的模式識(shí)別系統(tǒng)構(gòu)建主成分分析(PCA)和正交偏最小二乘(OPLS-DA)分析模型,進(jìn)行特異代謝物的過濾篩選,再利用二分類OPLS-DA模型中的變量投影重要性值(VIP)和VIP圖,載荷圖(S)對(duì)代謝標(biāo)志物進(jìn)一步篩選;初篩后的代謝物質(zhì)采用SPSS 21.0進(jìn)行獨(dú)立樣本非參數(shù)檢驗(yàn),鑒定特異性代謝標(biāo)志物;通過ROC曲線面積,評(píng)價(jià)特征性代謝物診斷結(jié)核性腦膜炎的診斷效能。結(jié)果:分別以TBM和N-TBM兩組的腦脊液和血清代謝物數(shù)據(jù)結(jié)果構(gòu)建OPLS-DA模型,發(fā)現(xiàn)可以很好地區(qū)分結(jié)核性腦膜炎組和非結(jié)核性腦膜炎組,該模型預(yù)測準(zhǔn)確度達(dá)到100%。腦脊液尋找到23個(gè)特征代謝物,發(fā)現(xiàn)了5個(gè)代謝物具有很好診斷效能;兩組血清篩出了31個(gè)特征離子,發(fā)現(xiàn)了6個(gè)代謝物具有很好診斷效能。腦脊液中的特征代謝離子包括番茄紅素甲酸脂(Methyl(7Z,9Z,9'Z)-6'-apo-ycaroten-6'-oate)、二氫順丁烯二酰亞胺β-D葡萄糖苷(Dihydromaleimide beta-Dglucoside)、去水山梨糖醇單油酸酯(Sorbitan oleate)、人參環(huán)氧炔醇亞油酸脂(Panaxydol linoleate)。血清中的可能特征代謝標(biāo)志物包括硬脂酸酰胺(Octadecanamide)、溶血磷脂酰膽堿(LysoPC(18:0))、磷脂酸20:4(5Z,8Z,11Z,14Z)e/2:0)、植烷酸、二十二烷酸6種代謝物有望成為結(jié)核腦膜炎的血清特異性診斷標(biāo)志物。結(jié)論:UPLC-MS的代謝組學(xué)研究技術(shù)結(jié)合正交偏最小二乘判別分析(OPLS-DA)模型的多元統(tǒng)計(jì)學(xué)分析方法,能夠發(fā)現(xiàn)與結(jié)核性腦膜炎的特異性強(qiáng)且有一定診斷效能的代謝產(chǎn)物,通過研究分析這些代謝產(chǎn)物在結(jié)核性腦膜炎的疾病發(fā)生發(fā)展過程中的產(chǎn)生機(jī)制,有助于對(duì)結(jié)核性腦膜炎的早期診斷,為臨床的靶向治療等進(jìn)一步研究提供理論依據(jù)和研究方向。
[Abstract]:Objective: To explore the specific metabolic substances in the cerebrospinal fluid and serum of patients with Tuberculous meningitis (TBM). Through the analysis and study of the changes in the number and nature of these metabolic substances in the patients, and the metabolic mechanisms in the process of disease evolution, a representative metabolic ion is sought to assist the clinical treatment of tuberculous brain. Early diagnosis and monitoring of the disease in order to improve the prognosis of the patients. Methods: a total of 47 specimens of cerebrospinal fluid (CSF) specimens and 107 serum samples were analyzed by the UPLC-MS (super high performance liquid chromatography and mass spectrometry) technique platform. The samples were taken from the cerebrospinal fluid of the patients in the Department of brain and tuberculosis of Tianjin Haihe Hospital in December November 2014. A total of 47 cases, including 21 cases of TBM, 26 cases of non tuberculous meningitis and 30 cases of health examination, were selected in 102 cases, including 57 male and 45 women, which were divided into 21 cases of tuberculous meningitis group, male / female 12/9, average age (48.01 + 12.35) years. The control group included non tuberculous meningitis group (group N-TBM) 26. There were 25 cases in the pulmonary tuberculosis group (group TB) and 30 cases in the healthy control group (group N). Among them, the male / female group in group N-TBM was 14/12, the average age was (45.56 + 19.43) years, including 7 cases of bacterial meningitis, 15 cases of viral meningitis, 4 cases of other causes of meningitis, and 25 cases in group TB, including 15 men, 10 women, average age (46.56 + 15.43) years, and healthy control groups, among them, among them a total of 30 cases in healthy control group, among them, healthy control group altogether 30 cases, among them, healthy control group altogether 30 cases, among them, healthy control group. There were 16 males and 14 females with an average age of (43.56 + 21.43) years. The detection of cerebrospinal fluid and serum samples were performed using Mzmine2.0 software by UPLC-MS. preliminary data processing. The primary processed data entered the SIMCA-P+12.0.1.0 software pattern recognition system to construct principal component analysis (PCA) and positive partial least squares (OPLS-DA) analysis model for specific metabolism. Filtering and screening of the material, then using the value of the variable projection value (VIP) and VIP diagram in the two classification OPLS-DA model, and the load map (S) to further screen the metabolic markers; the metabolic substances after the initial screening used SPSS 21 for the independent sample nonparametric test, identified the specific metabolites, and evaluated the characteristic metabolite diagnosis through the ROC curve area. The diagnostic effectiveness of tuberculous meningitis. Results: the OPLS-DA model was constructed with the results of TBM and N-TBM two groups of cerebrospinal fluid and serum metabolite data. It was found that the tuberculous meningitis group and non tuberculous meningitis group could be well divided. The prediction accuracy reached to the 100%. cerebrospinal fluid to find 23 Characteristic Metabolites and found 5 metabolites. The two groups of serum screened 31 characteristic ions and found that 6 metabolites have good diagnostic efficiency. The characteristic metabolic ions in the cerebrospinal fluid include lycopene formate (Methyl (7Z, 9Z, 9'Z) -6'-apo-ycaroten-6'-oate), and two HP Ding Xier imide beta -D glucoside (Dihydromaleimide beta-Dglucoside). Sorbitol mono oleate (Sorbitan oleate) and ginseng epoxy alkynol linoleic acid (Panaxydol linoleate). The possible characteristic metabolic markers in the serum include stearamide (Octadecanamide), lysophosphatidyl choline (LysoPC (18:0)), phosphatidic acid 20:4 (5Z, 8Z, 11Z, 14Z), and 6 metabolites of alkanoic acid and twenty-two alkanoic acid. Conclusion: the multivariate statistical analysis of UPLC-MS's metabonomics combined with orthogonal partial least squares discriminant analysis (OPLS-DA) model can detect the specific and diagnostic metabolites of tuberculous meningitis, and analyze these metabolites by analyzing these metabolites. The mechanism of the occurrence and development of tuberculous meningitis is helpful to the early diagnosis of tuberculous meningitis and to provide theoretical basis and research direction for further study of clinical target therapy.
【學(xué)位授予單位】：天津醫(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)】：R529.3

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