本文關(guān)鍵詞：小兒支氣管哮喘中醫(yī)證候?qū)W生物標(biāo)記物代謝組學(xué)研究　出處：《南京中醫(yī)藥大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 代謝組學(xué) 小兒支氣管哮喘 痰熱阻肺證 肺脾氣虛證 證候?qū)W標(biāo)記物

【摘要】：支氣管哮喘(Bronchial asthma)是威脅兒童健康最常見的慢性疾病。由于環(huán)境、生活方式改變等因素,我國小兒哮喘發(fā)病呈逐年上升趨勢,造成了巨大的家庭負(fù)擔(dān)。運(yùn)用中醫(yī)藥防治小兒哮喘歷史悠長,防治效果明顯,有著完善的理法方藥體系。目前兒童哮喘辨證多分為發(fā)作期、遷延期與緩解期三期,風(fēng)寒束肺證、痰熱阻肺證等八個證型。在臨床工作中,哮喘證型的判斷多依據(jù)醫(yī)師的個人經(jīng)驗(yàn),尚缺乏辨別不同證型的客觀化指標(biāo)。證候是中醫(yī)學(xué)中特有的名詞,在整個理論框架內(nèi)處于核心地位。加速中醫(yī)證候規(guī)范化建設(shè),實(shí)現(xiàn)證候的客觀化、標(biāo)準(zhǔn)化,是中醫(yī)學(xué)邁向科學(xué)化、走向世界的先決條件。本研究立足于中醫(yī)證候客觀化、標(biāo)準(zhǔn)化,以小兒支氣管哮喘為切入點(diǎn),采用代謝組學(xué)技術(shù)試圖揭示小兒哮喘不同證候間的物質(zhì)基礎(chǔ),是證候表征微觀化的一次有益的探索。目的:分析小兒哮喘發(fā)作期痰熱阻肺證、非痰熱阻肺證,緩解期肺脾氣虛證尿液樣本代謝譜,探尋小兒支氣管哮喘中醫(yī)證候?qū)W標(biāo)記物。方法:納入符合診斷標(biāo)準(zhǔn)的小兒哮喘發(fā)作期痰熱阻肺證24例、非痰熱阻肺證20例,緩解期肺脾氣虛證40例,同時納入健康小兒29例設(shè)為正常組。采集各組小兒尿液標(biāo)本進(jìn)行氣相色譜與質(zhì)譜聯(lián)用技術(shù)(Gas Chromatography-Mass Spectrometer/Mass Spectrometer,GC-MS/MS)檢測,同時將痰熱阻肺證、非痰熱阻肺證組尿液標(biāo)本進(jìn)行液相色譜與質(zhì)譜聯(lián)用技術(shù)(Liquid Chromatography-Mass Spectrometer/Mass Spectrometer,LC-MS/MS)檢測,將所得數(shù)據(jù)進(jìn)行正交偏最小二乘法(Orthogonal partial least squares-discriminant analysis,OPLS-DA)判別分析,變量重要性投影值(Variable importance in the projection,VIP)、非參數(shù)檢驗(yàn)以及XCMS Online分析平臺篩選、確定組間差異性代謝物,同時利用MetaboAnalyst平臺分析確定異常代謝通路。結(jié)果:各組間均能夠良好區(qū)分,一系列差異性代謝物及代謝通路被確定。1.與正常組相比,哮喘發(fā)作期患兒尿中肌醇、尿酸、硬脂酸等14種物質(zhì)的含量下降,氨基丙二酸含量升高;主要涉及丙酮酸代謝,賴氨酸降解、生物合成等5條代謝通路;2.與發(fā)作期非痰熱阻肺證組相比,GC-MS/MS結(jié)果顯示:痰熱阻肺證患兒尿中草酸、L-蘇氨酸、嘧啶等9種物質(zhì)的含量下降,主要涉及戊糖磷酸途徑,肌醇磷酸代謝4條等代謝通路。LC-MS/MS結(jié)果顯示:痰熱阻肺證患兒尿中蛋氨酸、琥珀酸、賴氨酸、肌酸、犬尿氨酸、環(huán)腺苷酸等多種有機(jī)酸、氨基酸,以及多種脂類、酮類化合物含量下降,僅羥基吲哚乙醛含量升高,主要涉及生物素代謝、色氨酸代謝等5條代謝通路。3.與肺脾氣虛證組相比,痰熱阻肺證患兒尿中氨基丙二酸、脯氨酸、苯丙氨酸、棕櫚酸等8種物質(zhì)含量升高,肌醇、尿酸、硬脂酸含量降低,主要涉及精氨酸和脯氨酸,甘氨酸、絲氨酸和蘇氨酸等4條代謝通路。結(jié)論:小兒哮喘發(fā)作期與健康小兒尿液代謝物具有差異;支氣管哮喘發(fā)作期不同證型、哮喘不同時期不同證型間存在代謝標(biāo)記物與代謝通路基礎(chǔ),可能是區(qū)分中醫(yī)不同證候的本質(zhì),通過進(jìn)一步驗(yàn)證優(yōu)化或可作為小兒哮喘中醫(yī)證候判斷生物學(xué)標(biāo)記物。
[Abstract]:Bronchial asthma (Bronchial asthma) is the most common chronic disease threat to children's health. Because of the environment, lifestyle changes and other factors, China's children with asthma increased year by year, caused a huge burden on the family. The use of Chinese medicine prevention and treatment of asthma in children has a long history, and obvious effect, with perfect prescription system at present children with asthma syndrome and more divided into the stage of attack and remission, delayed phase three, cold beam lung, syndrome of phlegm heat in the lung and other eight syndromes. In clinical work, on the basis of doctor's personal experience of asthma syndromes, lack of objective indicators to identify different types of syndromes. Is a noun characteristic in traditional Chinese medicine, is the core in the whole theoretical framework. To accelerate the construction of TCM standardization, to achieve the objective, the standardization of syndrome of traditional Chinese medicine, is a prerequisite to scientific, this study of the world. In TCM syndrome objective, standardized, in children with bronchial asthma as the breakthrough point, using metabonomics technology to reveal the material basis of different syndromes in children asthma, is a useful exploration of the characterization of Micro syndrome. Objective: analysis of phlegm heat obstructing lung syndrome in children asthma and non phlegm heat in the lung syndrome, alleviate lung temperdeficiency urine samples metabolic spectrum, explore the TCM syndrome of childhood bronchial asthma syndrome markers. Methods: patients met the diagnostic criteria of asthma in children 24 cases of phlegm heat in the lung syndrome onset, 20 cases of non phlegm heat in lung syndrome, lung and spleen qi deficiency syndrome remission in 40 cases, at the same time in healthy children 29 cases of normal group. Chromatography and mass spectrometry in urine specimens collected gas (Gas Chromatography-Mass Spectrometer/Mass Spectrometer, GC-MS/MS) detection, and the phlegm heat in lung syndrome, non phlegm heat in the lung syndrome group in urine specimens For liquid chromatography and mass spectrometry (Liquid Chromatography-Mass Spectrometer/Mass Spectrometer, LC-MS/MS) detection, the data of orthogonal partial least squares (Orthogonal partial least squares-discriminant analysis, OPLS-DA) discriminant analysis, variable importance projection value (Variable importance in the projection, VIP), non parametric test and XCMS Online analysis platform selection, determine the differences between groups of metabolites, and use the MetaboAnalyst platform to analyze and confirm the abnormal metabolic pathways. Results: both groups can good area, a series of specific metabolites and metabolic pathways were identified in.1. compared with the normal group, inositol, children with asthma in the urine uric acid, decreased content of stearic acid and other 14 kinds of substances, amino. Malonic acid content; mainly involved in pyruvate metabolism, lysine degradation, biological synthesis etc. 5 metabolic pathways; and 2. For non phlegm heat in the lung syndrome group compared to GC-MS/MS results showed that oxalic acid, phlegm heat in lung syndrome in children with urinary L- decreased content of threonine, pyrimidine and other 9 kinds of substances, mainly involved in the pentose phosphate pathway, inositol phosphate metabolism and other metabolic pathways of 4.LC-MS/MS showed that methionine, phlegm heat in lung syndrome in children with urinary succinate lysine, creatine, kynurenine, camp and other organic acids, amino acids, and a variety of lipids, decreased ketone content increased only hydroxyindole acetaldehyde content, mainly related to biological Sudache, compared tryptophan metabolism of 5 metabolic pathways of.3. with lung and spleen qi deficiency group, phlegm heat in lung syndrome in children with urinary in malonic acid, proline, phenylalanine, increased the content of 8 compounds of palmitic acid and inositol, uric acid, reduce the content of stearic acid, mainly involving arginine and proline, glycine, serine and threonine 4 metabolic pathways. Conclusion: Children with asthma and healthy children with urinary metabolite differences; period of different syndromes of asthma, metabolic markers and metabolic pathways of different syndromes of asthma in different periods, may be essential to distinguish different syndromes of traditional Chinese medicine, further tested through optimization or can be used as asthma syndromes to judge biological markers.

【學(xué)位授予單位】：南京中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R272

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王均衡;李英帥;駱斌;岳子敬;;陽虛體質(zhì)者糞便的代謝組學(xué)研究[J];北京中醫(yī)藥大學(xué)學(xué)報;2017年01期

2 王娟;馬素娜;謝世平;張寧;溫冠曉;張淼;張海燕;劉颯;劉偉;崔永霞;王海波;;基于液質(zhì)聯(lián)用技術(shù)艾滋病患者或艾滋病感染者肺脾氣虛證血液代謝組學(xué)研究[J];遼寧中醫(yī)雜志;2017年01期

3 李博林;王亞利;張明泉;王鑫國;賈琳;閆翠環(huán);曹文利;師旭亮;;衛(wèi)氣虛模型大鼠血漿代謝標(biāo)志物月節(jié)律變化的研究[J];中國中醫(yī)藥信息雜志;2016年11期

4 楊勇;;中醫(yī)證候模型建立的若干關(guān)鍵問題思考[J];中華中醫(yī)藥雜志;2016年10期

5 欒依含;劉先利;宗文靜;曹洪欣;;心血管病中醫(yī)證候蛋白質(zhì)組學(xué)研究概述[J];中國中醫(yī)基礎(chǔ)醫(yī)學(xué)雜志;2016年09期

6 于斌;厲啟芳;陳佳;吳先林;鄧力;趙昌林;陳孝銀;;流感病毒感染中醫(yī)證候動物模型建立方法及探討[J];時珍國醫(yī)國藥;2016年09期

7 李慧;王崢崢;郭自強(qiáng);;心梗后心衰大鼠中醫(yī)證候特點(diǎn)和“由瘀致虛”證動物模型的建立[J];北京中醫(yī)藥;2016年08期

8 馮文濤;蔡文君;陸施婷;陳茜蕾;劉國萍;;慢性胃炎中醫(yī)常見證候動物模型的研究進(jìn)展[J];中華中醫(yī)藥雜志;2016年07期

9 陳光;王階;高嘉良;董艷;;冠狀動脈粥樣硬化性心臟病血瘀證基因組學(xué)研究進(jìn)展[J];國際心血管病雜志;2016年02期

10 徐瑋斐;劉國萍;王憶勤;燕海霞;郭睿;;近5年中醫(yī)證候診斷客觀化研究述評[J];中醫(yī)雜志;2016年05期

，

本文編號：1425180