基于UPLC-MS技術(shù)的嬰兒巨細(xì)胞病毒肝炎濕熱內(nèi)蘊(yùn)證代謝模式研究
本文選題:嬰兒巨細(xì)胞病毒肝炎 切入點(diǎn):濕熱內(nèi)蘊(yùn)證 出處:《南京中醫(yī)藥大學(xué)》2016年碩士論文 論文類型:學(xué)位論文
【摘要】:巨細(xì)胞病毒(Cytomegalovirus,CMV)屬皰疹病毒p亞科,是先天性感染中較常見的病毒。我國(guó)是CMV感染的高發(fā)地區(qū),80%的小兒在3歲前已感染該病毒。CMV感染臨床發(fā)病及轉(zhuǎn)歸受到機(jī)體免疫力影響,在孕婦、嬰兒和免疫抑制的個(gè)體,可引起嚴(yán)重疾病,如胎兒畸形、嬰幼兒CMV肝炎、CMV肺炎、多器官功能損害等。嬰兒CMV肝炎是目前國(guó)內(nèi)最常見于嬰兒期的肝臟疾病,表現(xiàn)為黃疸消退延遲或逐漸加重,伴肝脾腫大及肝功能異常。肝臟炎癥較為嚴(yán)重的患兒出現(xiàn)肝纖維化,進(jìn)一步造成膽汁淤積。伴見膽道狹窄梗阻或膽道閉鎖的患兒預(yù)后較差。西醫(yī)治療該病以抗病毒藥物和對(duì)癥支持治療為主,效果不甚理想,且常用抗病毒藥物更昔洛韋存在骨髓抑制及肝、腎功能損害等不良反應(yīng),限制其臨床使用。本課題組長(zhǎng)期從事嬰兒CMV肝炎的基礎(chǔ)和臨床研究,對(duì)CMV的致病機(jī)理、病因病機(jī)、證候規(guī)律和中藥治療進(jìn)行了深入研究,但對(duì)于該病證型的證候本質(zhì)尚不清楚。本人所在的南京中醫(yī)藥大學(xué)中醫(yī)兒科學(xué)研究所具備較為完善的代謝組學(xué)分析平臺(tái),故本課題組采用代謝組學(xué)這一現(xiàn)代技術(shù)手段,結(jié)合臨床生化檢查,對(duì)CMV肝炎最常見的濕熱內(nèi)蘊(yùn)證進(jìn)行證本質(zhì)研究。目的:研究CMV肝炎濕熱內(nèi)蘊(yùn)證患兒血漿及尿液樣本的代謝產(chǎn)物,探求CMV肝炎濕熱內(nèi)蘊(yùn)證的證本質(zhì)。方法:搜集符合診斷標(biāo)準(zhǔn)的CMV肝炎濕熱內(nèi)蘊(yùn)證組患兒20例,同時(shí)搜集20例正常嬰兒設(shè)為正常組。分別采集兩組的血漿和尿樣,采用超高效液相色譜-二維線性離子阱質(zhì)譜聯(lián)用儀檢測(cè)兩組樣本,利用主成分分析和正交偏最小二乘法進(jìn)行統(tǒng)計(jì)分析,篩選潛在的差異性代謝物,分析差異代謝物的代謝通路,探求CMV肝炎濕熱內(nèi)蘊(yùn)證的證本質(zhì)。結(jié)果:1.血漿分析結(jié)果顯示,CMV肝炎濕熱內(nèi)蘊(yùn)證組和正常組OPLS-DA模型參數(shù)分別為R2Y=0.980,Q2=0.869(血漿上層樣本)和R2Y=0.950,Q2=0.898(血漿下層樣本)。正常組和CMV肝炎濕熱內(nèi)蘊(yùn)證組沿t[1]軸能完全分開,說明兩組的代謝模式存在明顯差異。共鑒定18個(gè)差異代謝物,其中SM(d18:1/18:0)、TG(16:0/18:1/14:1)、TG(16:0/18:1/18:0)等代謝物在患兒體內(nèi)呈上調(diào)趨勢(shì);DG(14:0/0:0/22:2)、TG(15:0/18:4/15:0)在患兒體內(nèi)呈下調(diào)趨勢(shì)。2.尿液分析結(jié)果顯示,CMV肝炎濕熱內(nèi)蘊(yùn)證組和正常組OPLS-DA模型參數(shù)分別為R2Y=0.882,Q2=0.835,正常組和CMV肝炎濕熱內(nèi)蘊(yùn)證組完全分開,說明兩組代謝產(chǎn)物差異顯著。最終鑒定出8個(gè)差異代謝物,其中Norvaline、Alanyl-Leucine等在患兒體內(nèi)呈上調(diào)趨勢(shì);Urocanic acid呈下調(diào)趨勢(shì)。結(jié)論:1.UPLC-LTQ/Orbitrap-MS技術(shù)能夠較好區(qū)分CMV肝炎濕熱內(nèi)蘊(yùn)證與正常嬰兒的代謝模式,并對(duì)CMV肝炎濕熱內(nèi)蘊(yùn)證的代謝模式進(jìn)行了初步闡釋。2.CMV肝炎濕熱內(nèi)蘊(yùn)證患兒血漿和尿液主要存在鞘脂代謝、甘油磷脂代謝及組氨酸代謝紊亂。
[Abstract]:Cytomegalovirus (CMV) belongs to the subfamily of herpesvirus p, which is a common virus in congenital infection. In China, 80% of children have been infected with CMV before the age of 3 years, and the clinical pathogenesis and outcome of CMV infection are affected by the immunity of the body. In pregnant women, infants and immunosuppressive individuals, it can cause serious diseases, such as fetal malformation, infantile CMV hepatitis pneumonia, multiple organ dysfunction and so on. Infantile CMV hepatitis is the most common liver disease in China at present. Jaundice was delayed or gradually aggravated, accompanied by hepatosplenomegaly and abnormal liver function. Liver fibrosis occurred in children with severe liver inflammation. The prognosis of children with biliary stricture obstruction or biliary atresia was poor. Western medicine was used to treat the disease mainly with antiviral drugs and symptomatic support. In addition, ganciclovir, a common antiviral drug, has adverse reactions such as bone marrow inhibition, liver and kidney function damage and so on, which restrict its clinical use. Our group has been engaged in the basic and clinical studies of infantile CMV hepatitis for a long time, and has been involved in the pathogenesis, etiology and pathogenesis of CMV. The syndromes and TCM treatment have been studied deeply, but the nature of syndromes of the syndrome type is not clear. The Institute of traditional Chinese Medicine and Pediatrics of Nanjing University of traditional Chinese Medicine has a relatively perfect platform for metabonomics analysis. Therefore, our group adopted the modern technique of metabonomics and combined with clinical biochemical examination. Objective: to study the metabolites of plasma and urine samples in children with CMV hepatitis with dampness and heat accumulation syndrome. To explore the syndromes essence of CMV hepatitis damp-heat accumulation. Methods: 20 cases of CMV hepatitis dampness and heat accumulation syndrome group were collected, and 20 normal infants were collected as normal group. Plasma and urine samples were collected from two groups, respectively. Two groups of samples were detected by ultra-high performance liquid chromatography-two-dimensional linear ion trap mass spectrometry. Principal component analysis (PCA) and orthogonal partial least square method were used for statistical analysis to screen potential differential metabolites and analyze metabolic pathways of differential metabolites. To explore the syndromes of CMV hepatitis dampness and heat accumulation. Results: 1. The results of plasma analysis showed that the parameters of OPLS-DA model of CMV hepatitis with damp-heat accumulation syndrome group and normal group were R2YP0. 980 Q2 0. 869 (plasma upper sample) and R2Y + 0. 950 Q 2 + 0. 898 (plasma substratum sample. Normal group and CMV liver group). The syndrome group of internal accumulation of inflammation, dampness and heat can be separated completely along the axis of t [1]. There were significant differences in metabolic patterns between the two groups. A total of 18 different metabolites were identified. Among them, the metabolites such as SMG18: 1 / 1 / 1 / 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1 / 1: 1: 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 0: 1: 1 / 1 / 1: 1: 1 / 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1: 1:. The results showed that there were significant differences in metabolites between the two groups. Finally, 8 different metabolites were identified. Among them, Norvaline Alanyl-Leucine showed an upward trend in children and Urocanic acid was down-regulated. Conclusion: 1. UPLC-LTQ / Orbitrap-MS technique can distinguish the damp heat accumulation of CMV hepatitis from the metabolic pattern of normal infants. The metabolic pattern of CMV hepatitis damp-heat accumulation syndrome was preliminarily explained. 2. There were mainly sphingolipid metabolism, glycerol phospholipid metabolism and histidine metabolism disorder in plasma and urine of children with CMV hepatitis damp-heat accumulation syndrome.
【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】:2016
【分類號(hào)】:R272
【相似文獻(xiàn)】
相關(guān)期刊論文 前10條
1 陳錦芳;徐韶連;;慢性非特異性潰瘍性結(jié)腸炎濕熱內(nèi)蘊(yùn)證結(jié)腸黏膜病理免疫特點(diǎn)研究[J];光明中醫(yī);2011年10期
2 肖超;呂照文;付肖冰;王真權(quán);李克亞;;復(fù)方芩柏顆粒劑保留灌腸治療慢性放射性直腸炎濕熱內(nèi)蘊(yùn)證30例臨床觀察[J];中醫(yī)藥導(dǎo)報(bào);2014年02期
3 王勇;謝世平;祝應(yīng)俊;陳曉輝;侯明杰;劉學(xué)偉;潘萬旗;許前磊;陳建設(shè);;艾滋病濕熱內(nèi)蘊(yùn)證和肺脾氣虛證主癥辨證第二輪專家問卷分析[J];遼寧中醫(yī)雜志;2012年01期
4 李國(guó)輝;趙福華;周小青;;脾胃濕熱證與氣象要素相關(guān)性初探[J];氣象與減災(zāi)研究;2010年04期
5 賀海輝;沈洪;鄭凱;顧培青;朱磊;劉亞軍;劉增巍;;清腸化濕方治療潰瘍性結(jié)腸炎活動(dòng)期濕熱內(nèi)蘊(yùn)證的療效觀察[J];中國(guó)中西醫(yī)結(jié)合雜志;2012年12期
6 鄭晨果;金純;葉樂馳;;葛仙湯治療潰瘍性結(jié)腸炎濕熱內(nèi)蘊(yùn)證臨床觀察[J];浙江中西醫(yī)結(jié)合雜志;2010年12期
7 伍群業(yè);;清腸湯合中藥灌腸對(duì)濕熱內(nèi)蘊(yùn)證潰瘍性結(jié)腸炎血沉和C-反應(yīng)蛋白的影響[J];中國(guó)中醫(yī)藥現(xiàn)代遠(yuǎn)程教育;2014年13期
8 謝靜,趙國(guó)榮,熊焰,李雅,陳蘭玲,黃裕洪;清熱解毒化濁片對(duì)慢性病毒性肝炎濕熱內(nèi)蘊(yùn)證、肝郁脾虛證療效的研究[J];湖南中醫(yī)學(xué)院學(xué)報(bào);2003年06期
9 許曉艷;楊強(qiáng);;清除幽門螺桿菌治療蕁麻疹2例[J];河南中醫(yī);2014年01期
10 ;[J];;年期
相關(guān)會(huì)議論文 前1條
1 沈洪;賀海輝;;清腸化濕法治療潰瘍性結(jié)腸炎活動(dòng)期濕熱內(nèi)蘊(yùn)證的療效觀察[A];中華中醫(yī)藥學(xué)會(huì)脾胃病分會(huì)第二十三次全國(guó)脾胃病學(xué)術(shù)交流會(huì)論文匯編[C];2011年
相關(guān)重要報(bào)紙文章 前1條
1 記者 黃心;國(guó)家中醫(yī)藥局印發(fā)災(zāi)害多發(fā)疾病中醫(yī)藥防治方案[N];中國(guó)中醫(yī)藥報(bào);2010年
相關(guān)碩士學(xué)位論文 前10條
1 馬杜彪;加味丹梔逍遙散治療急性痛風(fēng)性關(guān)節(jié)炎(濕熱內(nèi)蘊(yùn)證)的臨床研究[D];長(zhǎng)春中醫(yī)藥大學(xué);2015年
2 李維薇;基于UPLC-MS技術(shù)的嬰兒巨細(xì)胞病毒肝炎濕熱內(nèi)蘊(yùn)證代謝模式研究[D];南京中醫(yī)藥大學(xué);2016年
3 盛凌黎;正肝清黃片治療急慢性黃疸型病毒性肝炎(濕熱內(nèi)蘊(yùn)證)的臨床研究[D];湖北中醫(yī)學(xué)院;2008年
4 董發(fā)發(fā);清熱祛濕降濁湯治療慢性腎衰濕熱內(nèi)蘊(yùn)證的臨床研究[D];黑龍江省中醫(yī)藥科學(xué)院;2013年
5 武興偉;HIV/AIDS濕熱內(nèi)蘊(yùn)證轉(zhuǎn)錄組學(xué)研究[D];河南中醫(yī)學(xué)院;2013年
6 張敏;清熱祛濕湯治療潰瘍性結(jié)腸炎濕熱內(nèi)蘊(yùn)證的臨床研究[D];成都中醫(yī)藥大學(xué);2009年
7 賀海輝;清腸化濕法治療潰瘍性結(jié)腸炎活動(dòng)期濕熱內(nèi)蘊(yùn)證的療效觀察[D];南京中醫(yī)藥大學(xué);2011年
8 楊羅燕;自擬清化湯灌腸治療結(jié)直腸癌術(shù)后濕熱內(nèi)蘊(yùn)證的臨床研究[D];云南中醫(yī)學(xué)院;2014年
9 徐韶連;慢性非特異性潰瘍性結(jié)腸炎濕熱內(nèi)蘊(yùn)證腸黏膜病理及TNF-a、IL-8分泌水平研究[D];福建中醫(yī)藥大學(xué);2010年
10 盧茜;基于不同證型NAFLD相關(guān)因素的Logistic回歸分析及NAFLD血清GIP的研究[D];廣州中醫(yī)藥大學(xué);2011年
,本文編號(hào):1563098
本文鏈接:http://sikaile.net/yixuelunwen/eklw/1563098.html