肝衰竭患者呼出氣體中標志性化合物與血清生化指標的相關研究
本文選題:肝衰竭 + 呼出氣體; 參考:《南昌大學》2017年碩士論文
【摘要】:目的:應用封閉式電噴霧萃取電離質(zhì)譜法(EESI-MS)對健康志愿者和肝衰竭患者呼出氣體中標志性化合物進行檢測研究,并探索其與機體代謝及相應肝衰竭血清生化指標之間的聯(lián)系與差異。方法:1.分別收集肝衰竭患者(n=23)呼出氣和健康志愿者(n=25)的呼出氣,采用封閉式EESI-MS進行檢測。2.應用偏最小二乘法(PLS)對原始數(shù)據(jù)進行分析,挑選出有顯著差異的變量,在一級指紋譜圖中尋找其對應的高分辨分子質(zhì)量(m/z)。3.對差異變量對應的高分辨分子質(zhì)量進行二級串聯(lián)質(zhì)譜分析,鑒定其可能對應的化合物,并分析與肝衰竭的聯(lián)系。4.采用SPSS17.0軟件對呼氣中化合物分子質(zhì)量分別與肝衰竭生化指標如丙氨酸氨基轉移酶(ALT)、天門冬氨酸氨基轉移酶(AST)、總膽紅素(TB)、直接膽紅素(DB)、凝血酶原時間(PT)、凝血酶原活動度(PTA)進行統(tǒng)計分析。結果:1.采用偏最小二乘分析(PLS)處理數(shù)據(jù),發(fā)現(xiàn)健康志愿者和肝衰竭患者呼出氣體有較好的區(qū)分,利用模型變量VIP值挑選出24個導致差異最大的變量。2.對差異變量進行二級串聯(lián)質(zhì)譜分析,最終確定其10種化合物,分別為異丁烯(m/z 57),丙酮(m/z 59),乙醇醛(m/z 61),異戊二烯(m/z 69),2-丁酮(m/z 73),環(huán)戊酮(m/z 85),2,5-二甲基呋喃(m/z 97),2-乙基丙烯酸(m/z 101),6-甲基己烷-2-酮(m/z 115),辛醛(m/z 129)。3.通過對呼氣中化合物分子質(zhì)量與肝衰竭血清生化指標的分析,發(fā)現(xiàn)肝衰竭血清生化指標與相應的呼出氣體中化合物分子量呈線性相關。結論:1.肝衰竭患者和健康志愿者呼出氣體存在有差異的標志性化合物,其中鑒定出的有10種。異丁烯、丙酮、異戊二烯、2-丁酮、環(huán)戊酮及乙醇醛可推測出其在體內(nèi)的代謝過程及與疾病的關系。辛醛、2,5-二甲基呋喃、2-乙基丙烯酸和6-甲基己烷-2-酮仍需更多的研究。2.化合物分子質(zhì)量與肝衰竭嚴重程度呈正相關。肝衰竭越嚴重,肝衰竭患者體內(nèi)代謝越紊亂,呼出氣體中成分越復雜,與患者病情變化相符。
[Abstract]:Objective: to detect the characteristic compounds in the exhaled gases of healthy volunteers and patients with liver failure by closed electrospray extraction ionization mass spectrometry (EESI-MSMS). And to explore the relationship and difference between it and body metabolism and serum biochemical indexes of liver failure. Method 1: 1. The exhaled breath of patients with liver failure (n / n 23) and healthy volunteers (n / n = 25) were collected and detected by closed EESI-MS. The original data were analyzed by partial least square method (PLS), and the variables with significant difference were selected, and the corresponding high resolution molecular mass was found in the first order fingerprint spectrum. The high resolution molecular weight corresponding to the differential variables was analyzed by tandem mass spectrometry, and the possible corresponding compounds were identified, and the relationship between the molecular weight and liver failure was analyzed. Molecular weight of compounds in breath and biochemical parameters of liver failure, such as alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin, prothrombin activity, were determined by SPSS17.0 software. PTAs were used for statistical analysis. The result is 1: 1. The partial least square analysis was used to process the data, and it was found that there was a good distinction between healthy volunteers and patients with liver failure. The model variable VIP value was used to select 24 variables that led to the biggest difference. The differential variables were analyzed by two-stage tandem mass spectrometry, and 10 compounds were determined. They are isobutene / z / z 57, acetone / m / z 59, ethyl aldehydes / m / z / z 61, isoprene / m / z 69 and 2-butanone / m / z 73, cyclopentanone / z 85 / m / z, dimethyl furan / m / z 971 / z 971% / z 101mP / z 1011 / 6- methylhexane / 2-one / m / z 115n, octanal / mr / z 129n / m / 3. By analyzing the molecular weight of compounds in breath and serum biochemical indexes of liver failure, it was found that the molecular weight of compounds in the corresponding exhaled gases was linearly correlated with the serum biochemical indexes of liver failure. Conclusion 1. There were significant differences in the exhalation of gases between patients with liver failure and healthy volunteers, of which 10 were identified. Isobutene, acetone, isoprene 2-butanone, cyclopentanone and glycolaldehyde can infer its metabolic process in vivo and its relationship with disease. More studies are needed on 2-ethylacrylic acid and 6-methylhexane-2-one. The molecular weight of the compounds was positively correlated with the severity of liver failure. The more serious the liver failure, the more disorder the metabolism and the more complex the components in the exhaled gas, which are consistent with the changes of the patient's condition.
【學位授予單位】:南昌大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R575.3
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