本文選題：新生兒　切入點(diǎn)：腸道病毒　出處：《浙江大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景:每年的8～10月為腸道病毒感染的高發(fā)期,嬰幼兒是易感者。新生兒腸道病毒感染臨床表現(xiàn)輕重不一,且多樣化。先天性免疫反應(yīng)是機(jī)體抵抗細(xì)菌、病毒和真菌等各種病原微生物入侵的第一道防線,可快速識(shí)別病原微生物并對(duì)其作出應(yīng)答。Toll樣受體(TLR)是主要的模式識(shí)別受體,在先天性免疫應(yīng)答中識(shí)別各種病原微生物的保守結(jié)構(gòu),與多種細(xì)菌和病毒感染性疾病密切相關(guān)。TLR3主要負(fù)責(zé)識(shí)別病毒的雙鏈RNA和多聚肌胞苷酸,從而觸發(fā)炎癥反應(yīng)。近年來的研究發(fā)現(xiàn),TLR3在抗病毒免疫應(yīng)答中起重要作用,但目前其與腸道病毒感染的關(guān)系尚不清楚。本研究通過檢測(cè)TLR3基因rs3775296,rs3775292,rs3775291,rs3775290,rs13126816,rs5743312共六個(gè)位點(diǎn)的基因多態(tài)性,探討TLR3基因多態(tài)性與新生兒腸道病毒感染易感性的關(guān)系。目的:研究TLR3基因的遺傳多態(tài)性及其與新生兒腸道病毒感染的關(guān)系,探討腸道病毒的遺傳易感性以及細(xì)胞因子水平的變化。方法:選擇2013年5月一 2014年9月間在浙江大學(xué)醫(yī)學(xué)院附屬兒童醫(yī)院新生兒病房住院的47例新生兒腸道病毒感染患兒(病例組)和47例非感染性疾病患兒(對(duì)照組)為研究對(duì)象。留取其住院期間的血液標(biāo)本,提取基因組DNA,應(yīng)用聚合酶鏈反應(yīng)(PCR)技術(shù)分別檢測(cè)病例組及對(duì)照組TLR3基因rs3775296,rs3775292,rs3775291,rs3775290,rs13126816,rs5743312共六個(gè)位點(diǎn)的基因多態(tài)性,并利用DNA產(chǎn)物直接測(cè)序方法進(jìn)行序列分析,計(jì)算其基因型及等位基因頻率;并同時(shí)采用流式細(xì)胞術(shù)檢測(cè)兩組細(xì)胞因子(IL-2,IL-4,IL-6,IL-10,INF,IFN-r)水平的變化,并進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果:TLR3基因rs3775292位點(diǎn)有C和G兩種等位基因,其在心電圖異常組中的分布頻率分別為30%、70%,在心電圖正常組中的分布頻率分別為8%、92%,心電圖異常組與正常組相比,C等位基因和新生兒腸道病毒感染心電圖異常的風(fēng)險(xiǎn)有關(guān)(P0.05)。進(jìn)一步分析TLR3基因rs3775292位點(diǎn)的基因型頻率在心電圖異常組與正常組之間的分布差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);TLR3基因rs3775290,rs3775296,rs3775291,rs13126816,rs5743312五個(gè)位點(diǎn)的基因型和等位基因頻率在心電圖異常組與正常組之間的分布差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。TLR3基因rs3775296,rs3775292,rs3775291,rs3775290,rs13126816,rs5743312 六個(gè)位點(diǎn)的基因型和等位基因頻率在病例組和對(duì)照組之間、腦膜炎組與非腦膜炎組之間、發(fā)熱3天與≤3天組之間、血小板減少與正常組之間的分布差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。IL-6、IL-10等細(xì)胞因子水平病例組與對(duì)照組相比差異有統(tǒng)計(jì)學(xué)意義(P0.05)。IL-2,IL-4等細(xì)胞因子水平病例組與對(duì)照組基本持平,TNF,IFN-r等細(xì)胞因子水平在病例組雖有增高趨勢(shì),但與對(duì)照組相比差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:TLR3 基因 rs3775296,rs3775292,rs3775291,rs3775290,rs13126816,rs5743312六個(gè)SNP位點(diǎn)基因多態(tài)性可能與新生兒腸道病毒感染發(fā)病均無(wú)顯著關(guān)聯(lián),亦與新生兒腸道病毒感染腦膜炎發(fā)病、發(fā)熱持續(xù)時(shí)間、血小板減少病情均無(wú)顯著關(guān)聯(lián);rs3775292位點(diǎn)的C等位基因可能與新生兒腸道病毒感染心電圖異常的風(fēng)險(xiǎn)有關(guān)。新生兒腸道病毒感染時(shí)IL-6、IL-10多數(shù)有增高,IL-2,IL-4,TNF,IFN-r等細(xì)胞因子水平與新生兒腸道病毒感染無(wú)顯著關(guān)聯(lián)。
[Abstract]:Background: every 8~10 months for the high incidence of intestinal infection, infants and young children are susceptible to neonatal enterovirus infection. Clinical manifestations of varying severity, and diversification. The innate immune response is the first line of defense against bacteria, viruses and fungi and other pathogens, rapid identification of pathogenic microorganisms and make the response of.Toll like receptor (TLR) are pattern recognition receptors, conservative structure recognition of various pathogenic microorganisms in the innate immune response, double stranded RNA is closely related with various bacterial and viral infectious disease.TLR3 responsible for identification of viruses and poly I-C, thereby triggering inflammatory reaction. Research in recent years to found that TLR3 play an important role in antiviral immune response, but its relationship with intestinal infection is not clear. This study through the detection of TLR3 gene rs3775296, rs3775292, RS 3775291, rs3775290, rs13126816, rs5743312 gene polymorphism and six loci were, to investigate the TLR3 gene polymorphism and susceptibility of neonatal enterovirus infection. Objective: the relationship between the infection of genetic polymorphisms of TLR3 gene and neonatal enterovirus, to explore the genetic susceptibility of intestinal virus and changes in cytokine levels. Methods: in May 2013 a September 2014 at the children's Hospital Affiliated to Medical College of Zhejiang University in 47 hospitalized cases of neonatal enterovirus infection (case group) and 47 cases of non infectious diseases (control group) as the research object. The blood samples taken during the stay in hospital, to extract genomic DNA by polymerase chain reaction (PCR) technology were detected in case group and control group TLR3 gene rs3775296, rs3775292, rs3775291, rs3775290, rs13126816, rs5743312 gene polymorphism in six sites, And the sequence was analyzed by direct sequencing method of DNA product, calculate the genotype and allele frequency; and at the same time using flow cytometry in two group of cytokines (IL-2, IL-4, IL-6, IL-10, INF, IFN-r) level, and statistical analysis. Results: TLR3 gene locus rs3775292 and C the two alleles of G, the abnormal ECG group frequency distribution were 30%, 70%, the frequency distribution in normal ECG group were 8%, 92%, abnormal ECG group compared with normal group, the risk of abnormal ECG C allele and neonatal enterovirus infection (P0.05) for further analysis. Differences in genotype frequencies of TLR3 gene rs3775292 locus between abnormal ECG group and normal group had no statistical significance (P0.05); TLR3 gene rs3775290, rs3775296, rs3775291, rs13126816, rs5743312 five locus genotype and allele Because of the difference in frequency distribution between the abnormal ECG group and normal group were not statistically significant (P0.05).TLR3 gene rs3775296, rs3775292, rs3775291, rs3775290, rs13126816, rs5743312 six locus genotype and allele frequencies between case group and control group, between meningitis group and non meningitis group, between the fever for 3 days with less than 3 days, the distribution difference between thrombocytopenia and normal group were not statistically significant (P0.05.IL-6), IL-10 cell factor level in case group compared with the control group, the difference was statistically significant (.IL-2, P0.05) IL-4 cell factor level in the case group and the control group was essentially flat, TNF, IFN-r and other cytokines in case group has increased, but compared with the control group showed no significant difference (P0.05). Conclusion: TLR3 gene rs3775296, rs3775292, rs3775291, rs3775290, rs13126816, rs5743312 six SNP loci There were no significant association of gene polymorphism may be associated with neonatal enterovirus infection and neonatal enterovirus infection meningitis, duration of fever, thrombocytopenia patients showed no significant correlation; rs3775292 loci of the C allele may be associated with neonatal enterovirus infection risk of abnormal ECG. Neonatal enterovirus infection IL-6, IL-10 most there is increased, IL-2, IL-4, TNF, IFN-r etc. but there was no significant association between cytokine levels and intestinal virus infection of the newborn.

【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R722.1

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