小兒病毒性肺炎風(fēng)寒郁肺證的代謝組學(xué)研究
發(fā)布時(shí)間：2018-07-23 14:12
【摘要】：背景:兒童社區(qū)獲得性肺炎(CAP)已經(jīng)逐漸成為導(dǎo)致全世界5歲以下兒童死亡的第一位病因。全球每年死于肺炎的患兒統(tǒng)計(jì)數(shù)據(jù)大約是200萬(wàn),這占到全球范圍內(nèi)兒童死亡總數(shù)的200%。病毒感染是小兒CAP區(qū)別于成人的重要特征。其中以呼吸道合胞病毒(Respiratory Syncytia1 Virus;RSV)占首位[1],其他病毒如腺病毒(Adenovirus,ADV)、流感病毒(Inf1uenza virus,IFV)、人類(lèi)偏肺病毒(Human meta-pneumoniae virus,hMPV)副流感病毒(Parainfluenza virus,PIV)等。就中醫(yī)病名而言,兒童CAP可劃為"肺炎喘嗽",風(fēng)寒郁肺證常作為小兒病毒性肺炎起初的重要證候,如何全面地、科學(xué)地闡述這一中醫(yī)證候內(nèi)涵與本質(zhì),成為現(xiàn)代中醫(yī)學(xué)需解決的迫切問(wèn)題。據(jù)相應(yīng)的研究顯示,兒童病毒性肺炎的治療上,缺乏完全有效、安全的理想化合藥物,病毒唑(Ribavirin)是唯一被美國(guó)兒科協(xié)會(huì)(AAP)謹(jǐn)慎推薦的"也許能夠使用"的合成核苷類(lèi)抗病毒藥物。相較于此,中醫(yī)藥在治療小兒病毒性肺炎上顯示出明顯優(yōu)勢(shì),且已經(jīng)為大量臨床和實(shí)驗(yàn)研究所證實(shí)。代謝組學(xué)(Metabolomics)作為系統(tǒng)生物學(xué)的重要組成部分,是聚焦于生物體內(nèi)源性代謝物性質(zhì)、數(shù)量、種類(lèi)及其整體變化規(guī)律的一門(mén)嶄新學(xué)科[2]。代謝組學(xué)可以有效避免既往蛋白組學(xué)或基因組學(xué)單獨(dú)采用一種或幾種指標(biāo),或者一條或幾條基因阻斷后的通路表達(dá)就預(yù)測(cè)或推斷生理狀態(tài)或病理情況的"真實(shí)世界",同時(shí)卻可以及時(shí)地、有效地、客觀(guān)靈敏地映射生物體受外界擾動(dòng)后機(jī)體內(nèi)基因、蛋白、細(xì)胞或組織的"生化表型",以整體衡量取代單一檢測(cè),這十分契合中醫(yī)基礎(chǔ)理論的"整體觀(guān)、恒動(dòng)觀(guān)",是一種以"航拍視覺(jué)"替換單一"叢林搜索"的角度�；诖朔N宏觀(guān)認(rèn)識(shí),本課題采用代謝組學(xué)方法,結(jié)合患兒生命體征,血、尿常規(guī),肝、腎功能等生化檢測(cè),整體出發(fā)探討病毒性肺炎風(fēng)寒郁肺證(WC)所導(dǎo)致的代謝差異的意義,試圖從小分子代謝角度解釋小兒病毒性肺炎風(fēng)寒郁肺證的證候內(nèi)涵。目的：整體角度探討小兒病毒性肺炎風(fēng)寒郁肺證患兒的血清和尿液的內(nèi)源性差異代謝特征,闡釋小兒病毒性肺炎風(fēng)寒郁肺證的差異代謝證候?qū)嵸|(zhì)。方法:小兒病毒性肺炎風(fēng)寒郁肺證組學(xué)技術(shù)的臨床實(shí)驗(yàn):挑選可以納入中西醫(yī)診斷標(biāo)準(zhǔn)的病毒性肺炎屬于風(fēng)寒郁肺證型的患兒30例,設(shè)為風(fēng)寒組(WC),同時(shí)設(shè)立體檢時(shí)的正常健康兒童30例(NH)。分別在入院第二天收集兩組兒童的血清和尿液,采用氣相色譜-質(zhì)譜聯(lián)用儀(Gas-Chromatography-MassSpectrometry,GC-MS)同時(shí)分析獲取WC組和NH組血清、尿液中的差異內(nèi)源性代謝物,基于數(shù)據(jù)庫(kù)成立小兒病毒性肺炎風(fēng)寒郁肺證的證候相關(guān)代謝集群,通過(guò)在線(xiàn)分析平臺(tái)XCMS Online預(yù)處理、NIST數(shù)據(jù)庫(kù)和已有標(biāo)準(zhǔn)品進(jìn)行驗(yàn)證、MetaboAnalyst確定差異性代謝物及代謝路徑,解釋所涉及的相關(guān)通路,揭示小兒病毒性肺炎風(fēng)寒郁肺證的差異代謝特點(diǎn)和本質(zhì)。結(jié)果:1.血清代謝組學(xué)模式識(shí)別分析結(jié)果顯示,風(fēng)寒郁肺證與健康兒童組間能夠良好區(qū)分,眾多有機(jī)酸、氨基酸、脂類(lèi)等差異性代謝物及代謝通路被確定。與健康兒童相比,風(fēng)寒郁肺證患兒血清中丙氨酸、天冬氨酸、谷氨酸、甘氨酸、絲氨酸、蘇氨酸、�；撬帷①�(lài)氨酸等多種有機(jī)酸、氨基酸上調(diào);氨基丁酸、乙醇酸、甘油、1-棕櫚酸單甘油酯、膽固醇、葡萄糖等下調(diào)。2.尿液代謝組學(xué)模式識(shí)別分析結(jié)果顯示,風(fēng)寒郁肺證與健康兒童組間雖有一定分離趨勢(shì),但仍存在交叉重疊,進(jìn)一步建模OPLS-DA,兩組完全分離,說(shuō)明代謝物存在差異。尿液代謝中甘氨酸、絲氨酸、色氨酸、β-羥基丁酸、葡萄糖酸、D-半乳糖、肌苷、尿苷等物質(zhì)上調(diào);羥基乙酸、硬脂酸、棕櫚酸等下調(diào)。結(jié)論:1.GC-MS代謝組學(xué)技術(shù)平臺(tái)能夠良好區(qū)分和初步解答小兒病毒性肺炎風(fēng)寒郁肺證(WC)與正常健康兒(NH)之間的差異代謝。2.病毒性肺炎WC證患兒的血清和尿液代謝中主要以丙氨酸、甘氨酸、�；撬岽x、花生四烯酸、棕櫚酸代謝等代謝紊亂為標(biāo)志。
[Abstract]:Background: Children's community-acquired pneumonia (CAP) has gradually become the first cause of death in children under 5 years of age. The statistics of children who die of pneumonia every year around the world are about 2 million. This accounts for the 200%. virus infection of the total number of children in the world, which is an important feature of children's CAP different from adults. Respiratory Syncytia1 Virus (RSV) accounts for the first [1], other viruses such as Adenovirus (ADV), influenza virus (Inf1uenza virus, IFV), human partial lung virus (Human meta-pneumoniae) parainfluenza virus (Human meta-pneumoniae), etc. As an important symptom of viral pneumonia at the beginning of children, how to comprehensively and scientifically explain the connotation and essence of the TCM syndrome has become an urgent problem to be solved in modern Chinese medicine. According to the corresponding research, the treatment of viral pneumonia in children is lack of complete effective, safe and ideal combination drug, and Ribavirin is the only one. AAP, which is carefully recommended by the American paediatrics Association, "may be able to use" synthetic nucleoside antiviral drugs. Compared with this, traditional Chinese medicine has shown obvious advantages in the treatment of viral pneumonia in children, and has been confirmed by a large number of clinical and experimental studies. Metabolomics (Metabolomics) is an important component of system biology. A new subject, [2]. metabolomics, which is a new subject in the nature of endogenous metabolites, quantity, species, and overall changes of organisms. It can effectively avoid the previous proteomics or genomics by using one or several indicators, or the expression of one or several genes blocking the pathway to predict or infer physiological or pathological conditions. "Real world", at the same time, it can be timely, effectively and objectively and sensitively map the organism, protein, cell or tissue "biochemical phenotypes" in the body after disturbance, and replace the single detection by the whole measure. This fits the basic theory of traditional Chinese medicine, the concept of holism, the concept of constant motion, is a kind of "aerial vision" replacing a single "jungle search". On the basis of this macro understanding, this subject uses the metabonomics method, combined with the biochemical tests of children's life signs, blood, urine routine, liver and kidney function, and discusses the significance of metabolic difference caused by the WC of viral pneumonia and wind cold depression, and tries to explain the syndrome of the wind cold and depressed lung syndrome of children with viral pneumonia from an early age. Objective: To explore the endogenous differential metabolism characteristics of serum and urine in children with viral pneumonia, wind cold and depression, and to explain the essence of differential metabolic syndrome in children with viral pneumonia, wind cold and depressed lung syndrome. Methods: clinical experiment of children viral pneumonia in wind cold depression and lung syndrome: selection can be included in Chinese and Western medicine. The standard viral pneumonia belongs to 30 children with wind cold and lung syndrome type, which is set as the wind cold group (WC). At the same time, 30 cases of normal healthy children (NH) were set up at the physical examination. The serum and urine of two groups of children were collected for second days in the hospital, and the WC group was obtained by gas chromatography-mass spectrometry (Gas-Chromatography-MassSpectrometry, GC-MS) simultaneously. The difference of endogenous metabolites in the serum and urine of NH group, based on the database to establish the syndrome related metabolic clusters of children with viral pneumonia, wind cold and depression, was pretreated by the online analysis platform XCMS Online, the NIST database and the existing standard, and MetaboAnalyst to determine the differential metabolites and metabolic pathways. The related pathways were used to reveal the characteristics and nature of the differential metabolism of the wind cold and depressed lung syndrome in children. Results: 1. the results of the pattern recognition analysis showed that the wind cold and the lung syndrome can distinguish well between the healthy children and the healthy children, and many organic acids, amino acids, lipids and other metabolites and metabolic pathways were determined. Compared with healthy children, The serum alanine, aspartic acid, glutamic acid, glycine, serine, threonine, taurine, lysine and other organic acids are up regulated in the serum of children with wind cold and depressed lung syndrome, and the amino acid up-regulation of amino acids, such as aminobutyric acid, glycolic acid, glycerol, 1- palmitate monoglyceride, cholesterol, glucose and other.2. urine metabolomics pattern recognition analysis results show that wind cold and depressed lung syndrome and Although there is a certain separation trend among the healthy children, there are still overlapping overlapping, further modeling OPLS-DA, the two groups are completely separated, indicating that there are differences in metabolites. In urine metabolism, glycine, serine, tryptophan, beta hydroxybutyric acid, gluconic acid, D- galactose, inosine, uridine and so on are up-regulated, and hydroxyacetic acid, stearic acid, palmitic acid and so on are down regulated. The 1.GC-MS metabonomics technology platform can distinguish and preliminarily solve the differential metabolism between WC and normal healthy children (NH). The serum and urine metabolism of WC syndrome in children with.2. virus pneumonia are mainly metabolic disorders such as alanine, glycine, bovine sulfonic acid metabolism, peanut four enoic acid, palmitic acid metabolism and other metabolic disorders. Mark.
【學(xué)位授予單位】：南京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R272
本文編號(hào)：2139666
[Abstract]:Background: Children's community-acquired pneumonia (CAP) has gradually become the first cause of death in children under 5 years of age. The statistics of children who die of pneumonia every year around the world are about 2 million. This accounts for the 200%. virus infection of the total number of children in the world, which is an important feature of children's CAP different from adults. Respiratory Syncytia1 Virus (RSV) accounts for the first [1], other viruses such as Adenovirus (ADV), influenza virus (Inf1uenza virus, IFV), human partial lung virus (Human meta-pneumoniae) parainfluenza virus (Human meta-pneumoniae), etc. As an important symptom of viral pneumonia at the beginning of children, how to comprehensively and scientifically explain the connotation and essence of the TCM syndrome has become an urgent problem to be solved in modern Chinese medicine. According to the corresponding research, the treatment of viral pneumonia in children is lack of complete effective, safe and ideal combination drug, and Ribavirin is the only one. AAP, which is carefully recommended by the American paediatrics Association, "may be able to use" synthetic nucleoside antiviral drugs. Compared with this, traditional Chinese medicine has shown obvious advantages in the treatment of viral pneumonia in children, and has been confirmed by a large number of clinical and experimental studies. Metabolomics (Metabolomics) is an important component of system biology. A new subject, [2]. metabolomics, which is a new subject in the nature of endogenous metabolites, quantity, species, and overall changes of organisms. It can effectively avoid the previous proteomics or genomics by using one or several indicators, or the expression of one or several genes blocking the pathway to predict or infer physiological or pathological conditions. "Real world", at the same time, it can be timely, effectively and objectively and sensitively map the organism, protein, cell or tissue "biochemical phenotypes" in the body after disturbance, and replace the single detection by the whole measure. This fits the basic theory of traditional Chinese medicine, the concept of holism, the concept of constant motion, is a kind of "aerial vision" replacing a single "jungle search". On the basis of this macro understanding, this subject uses the metabonomics method, combined with the biochemical tests of children's life signs, blood, urine routine, liver and kidney function, and discusses the significance of metabolic difference caused by the WC of viral pneumonia and wind cold depression, and tries to explain the syndrome of the wind cold and depressed lung syndrome of children with viral pneumonia from an early age. Objective: To explore the endogenous differential metabolism characteristics of serum and urine in children with viral pneumonia, wind cold and depression, and to explain the essence of differential metabolic syndrome in children with viral pneumonia, wind cold and depressed lung syndrome. Methods: clinical experiment of children viral pneumonia in wind cold depression and lung syndrome: selection can be included in Chinese and Western medicine. The standard viral pneumonia belongs to 30 children with wind cold and lung syndrome type, which is set as the wind cold group (WC). At the same time, 30 cases of normal healthy children (NH) were set up at the physical examination. The serum and urine of two groups of children were collected for second days in the hospital, and the WC group was obtained by gas chromatography-mass spectrometry (Gas-Chromatography-MassSpectrometry, GC-MS) simultaneously. The difference of endogenous metabolites in the serum and urine of NH group, based on the database to establish the syndrome related metabolic clusters of children with viral pneumonia, wind cold and depression, was pretreated by the online analysis platform XCMS Online, the NIST database and the existing standard, and MetaboAnalyst to determine the differential metabolites and metabolic pathways. The related pathways were used to reveal the characteristics and nature of the differential metabolism of the wind cold and depressed lung syndrome in children. Results: 1. the results of the pattern recognition analysis showed that the wind cold and the lung syndrome can distinguish well between the healthy children and the healthy children, and many organic acids, amino acids, lipids and other metabolites and metabolic pathways were determined. Compared with healthy children, The serum alanine, aspartic acid, glutamic acid, glycine, serine, threonine, taurine, lysine and other organic acids are up regulated in the serum of children with wind cold and depressed lung syndrome, and the amino acid up-regulation of amino acids, such as aminobutyric acid, glycolic acid, glycerol, 1- palmitate monoglyceride, cholesterol, glucose and other.2. urine metabolomics pattern recognition analysis results show that wind cold and depressed lung syndrome and Although there is a certain separation trend among the healthy children, there are still overlapping overlapping, further modeling OPLS-DA, the two groups are completely separated, indicating that there are differences in metabolites. In urine metabolism, glycine, serine, tryptophan, beta hydroxybutyric acid, gluconic acid, D- galactose, inosine, uridine and so on are up-regulated, and hydroxyacetic acid, stearic acid, palmitic acid and so on are down regulated. The 1.GC-MS metabonomics technology platform can distinguish and preliminarily solve the differential metabolism between WC and normal healthy children (NH). The serum and urine metabolism of WC syndrome in children with.2. virus pneumonia are mainly metabolic disorders such as alanine, glycine, bovine sulfonic acid metabolism, peanut four enoic acid, palmitic acid metabolism and other metabolic disorders. Mark.
【學(xué)位授予單位】：南京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R272
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 任靖;汪受傳;張秋月;翟文生;賴(lài)子娟;單進(jìn)軍;;兒童病毒性肺炎風(fēng)寒郁肺證代謝組學(xué)研究[J];南京中醫(yī)藥大學(xué)學(xué)報(bào);2017年02期
2 湯文天;王靜;劉駿;陸曉華;王國(guó)光;姜玉新;;�；撬釡p輕內(nèi)毒素誘導(dǎo)的大鼠心肌損傷[J];中國(guó)病理生理雜志;2017年01期
3 李武國(guó);劉嘉煒;李慶國(guó);葉玉珊;司馬貞華;;虎杖根莖超臨界CO_2萃取物GC/MS分析及抗細(xì)胞遷移活性評(píng)價(jià)[J];質(zhì)譜學(xué)報(bào);2014年05期
4 林浩;吳金勇;李燕寧;;李燕寧教授“三關(guān)”論治肺炎學(xué)術(shù)思想探討[J];中國(guó)中西醫(yī)結(jié)合兒科學(xué);2014年02期
5 閆永彬;馬淑霞;丁櫻;;從熱飲論治小兒肺炎初期[J];中國(guó)中醫(yī)基礎(chǔ)醫(yī)學(xué)雜志;2014年02期
6 賈偉;敖平;王曉艷;;代謝組學(xué):系統(tǒng)生物醫(yī)學(xué)的關(guān)鍵角色[J];科學(xué);2012年06期
7 段林建;張清;王農(nóng)榮;楊斌;何士勤;孫堅(jiān);;連翹苷對(duì)甲型流感病毒核蛋白基因表達(dá)的影響研究[J];中國(guó)全科醫(yī)學(xué);2012年18期
8 鄒忠杰;龔夢(mèng)鵑;謝媛媛;王淑美;梁生旺;;氫化可的松誘導(dǎo)的腎陽(yáng)虛大鼠尿液代謝組學(xué)研究[J];中國(guó)實(shí)驗(yàn)方劑學(xué)雜志;2012年08期
9 楊燕;汪受傳;李瑞麗;白文靜;;清開(kāi)靈注射液治療小兒RSV肺炎痰熱閉肺證主癥不同時(shí)點(diǎn)的療效[J];中國(guó)中西醫(yī)結(jié)合雜志;2010年09期
10 陳琴華;李鵬;彭林;朱軍;李志浩;;氣相色譜—質(zhì)譜聯(lián)用法在體內(nèi)藥物分析中的應(yīng)用[J];中國(guó)醫(yī)院藥學(xué)雜志;2010年03期
，本文編號(hào)：2139666
本文鏈接：http://sikaile.net/shoufeilunwen/mpalunwen/2139666.html
最近更新
教材專(zhuān)著
