本文選題：乙型肝炎病毒　切入點(diǎn)：疫苗　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：第一部分1-16歲兒童乙肝疫苗接種后抗體水平變化規(guī)律分析目的:接種乙肝疫苗是目前預(yù)防乙型肝炎病毒感染(Hepatitis B Virus,HBV)最有效的方法,乙肝疫苗接種政策的實(shí)施顯著降低了我國一般人群HBV感染率。這部分旨在分析1-16歲住院兒童嬰幼兒期乙肝疫苗接種后抗體水平隨年齡增長(zhǎng)變化規(guī)律,評(píng)估接種加強(qiáng)針的必要性。方法:根據(jù)重慶醫(yī)科大學(xué)附屬兒童醫(yī)院((Children’s Hospital of Chongqing Medical University,CHCMU)臨床檢驗(yàn)中心對(duì)93,326名1-16歲住院兒童乙肝標(biāo)志物包括乙肝表面抗體(Hepatitis B Surface Antibody,HBs Ab),乙肝表面抗原(Hepatitis B Surface Antigen,HBs Ag)和乙肝核心抗體(Hepatitis B core Antibody HBc Ab)的檢查結(jié)果,分析anti-HBs滴度變化規(guī)律及HBs Ag和HBc Ab的攜帶率。結(jié)果:93326名1-16歲住院兒童中HBs Ag和HBc Ab攜帶率分別為0.48%和4.05%。保護(hù)性抗體水平比例表現(xiàn)出先下降后上升的趨勢(shì),1歲年齡組血清保護(hù)率最高(90.31%),8歲年齡組最低(45.29%);所有年齡組兒童保護(hù)性抗體水平比例在45.29%-63.33%之間除1-3歲年齡組外(90.31%,83.95%和71.82%);絕大部分年齡組中高等抗體反應(yīng)者比例在5.03%-10.56%之間;所有年齡組中沒有發(fā)生血清轉(zhuǎn)換的比例在3.33%-25.79%之間;男女之間抗體水平無顯著統(tǒng)計(jì)學(xué)差異(p0.05)。有明確再接種史兒童抗體幾何平均滴度(Geometric Mean Titers,GMT)顯著高于不清楚是否有再接種及無再接種史兒童,前者與后兩者相比均具有顯著統(tǒng)計(jì)學(xué)差異(p0.0001),不清楚是否有再接種史兒童GMT也顯著高于無再接種史兒童抗體水平(p0.05)。結(jié)論:我們通過大樣本連續(xù)年齡段對(duì)出生后在嬰幼兒期完成初次免疫接種的兒童調(diào)查研究發(fā)現(xiàn)1-16歲兒童總體抗體保護(hù)率為67.10%,1-8歲年齡組兒童中保護(hù)性抗體水平比例從90.31%下降至45.29%,而9-15歲年齡組中其抗體陽性率又從45.46%上升至63.33%,高等抗體水平者比例在大部分年齡組中保持相對(duì)穩(wěn)定,沒有表現(xiàn)出明顯的下降或上升。接種加強(qiáng)針會(huì)顯著增加抗體濃度,對(duì)沒有發(fā)生抗體血清轉(zhuǎn)換者建議再接種加強(qiáng)針,尤其是這些在學(xué)校住宿或者家庭成員中有HBs Ag攜帶者的兒童。第二部分乙肝病毒母嬰傳播免疫逃逸機(jī)制初步探討目的:母嬰傳播是乙肝病毒最主要的傳播方式,這部分主要探討母親為HBs Ag攜帶者所生新生兒在主被動(dòng)免疫后仍然發(fā)展為慢性感染的高危因素,為進(jìn)一步控制乙肝病毒母嬰傳播(Mother to Child Transmission,MTCT)提供參考。方法:收集母親及孩子均攜帶HBs Ag、母親攜帶HBs Ag而孩子健康和母親及孩子均健康的母親血液提取RNA,RNA經(jīng)逆轉(zhuǎn)錄為c DNA后通過RT2 Profiler PCR Array和Affymetrix Prime View Human Gene Expression Array篩選具有顯著差異表達(dá)基因。結(jié)果:參與固有免疫反應(yīng)的84種關(guān)鍵基因篩查中共有11個(gè)基因有差異表達(dá),其中上調(diào)的有9個(gè),下調(diào)的有2個(gè)。人表達(dá)譜芯片可檢測(cè)的基因數(shù)有20000個(gè),通過分析發(fā)現(xiàn)8種可能與HBV母嬰傳播相關(guān)的基因,其中有1個(gè)基因表現(xiàn)為上調(diào),7個(gè)基因表現(xiàn)為下調(diào)。結(jié)論:篩選出的差異表達(dá)基因參與固有免疫反應(yīng)、細(xì)胞信號(hào)傳導(dǎo)、細(xì)胞遷移、血管生成、凋亡、癌癥發(fā)生等多種生物過程,它們可能在乙肝病毒母嬰傳播中發(fā)揮重要作用,需更多標(biāo)本驗(yàn)證這一結(jié)果并發(fā)現(xiàn)可能的機(jī)制。
[Abstract]:The first part of the 1-16 year old children after hepatitis B vaccination antibody changes analysis objective: hepatitis B vaccination is the prevention of hepatitis B virus infection (Hepatitis B, Virus, HBV) the most effective method, the implementation of hepatitis B vaccination policies significantly reduced the Chinese general population infection rate of HBV. This part aims at the analysis of 1-16 hospitalized children infant hepatitis B vaccine antibody level changes with age, the necessity to strengthen the assessment of vaccination needle. Methods: according to the children's Hospital Affiliated to Medical University Of Chongqing ((Children s Hospital of Chongqing Medical University ', CHCMU) clinical inspection center on the 93326 1-16 year old children hospitalized for hepatitis B markers including hepatitis B surface antibody (Hepatitis B Surface Antibody HBs, Ab), hepatitis B surface antigen (Hepatitis B Surface Antigen, HBs Ag) and hepatitis B core antibody (Hepatitis B core Antibody HB C Ab) test results, analysis the carrying rate variation of anti-HBs Ag and HBc Ab titer and HBs. Results: 93326 1-16 year old children hospitalized in HBs Ag and HBc Ab carrying rate were 0.48% and 4.05%. protective antibody levels in proportion showed upward trend after the first drop, 1 year old age group serum protection rate the highest (90.31%), 8 year old age group was the lowest (45.29%); all age groups of children protective antibody levels between the proportion of 45.29%-63.33% in addition to 1-3 years age group (90.31%, 83.95% and 71.82%); the vast proportion of higher antibody response in most age groups in 5.03% -10.56% among all age groups; no seroconversion the proportion between 3.33%-25.79%; there was no statistically significant difference in antibody levels between men and women (P0.05). A clear history of children's vaccination with geometric mean titers (Geometric Mean, Titers, GMT) is not clear whether there is no vaccination and was significantly higher than that of Vaccinated children, the former and the latter two were compared with significant statistical difference (P0.0001), do not know whether there re vaccination history children GMT is significantly higher than that of no vaccination history of children's antibody level (P0.05). Conclusion: we are using a large sample of children ages of continuous investigation was born after the completion of initial immunization in infant period the discovery of 1-16 year old children overall antibody protection rate was 67.10%, antibody levels decreased from 90.31% to 45.29% to protect the 1-8 age group of children, and the antibody positive rate of 9-15 year old age group and increased from 45.46% to 63.33%, the proportion of high antibody level remained relatively stable in most age groups, showed no obviously decreased or increased. Vaccination strengthen a needle will significantly increase in antibody concentration of no antibody seroconversion suggested to strengthen vaccination needle, especially those in the school or family members There are HBs Ag carriers. Second children escape mechanism part of maternal transmission of hepatitis B virus immune to investigate: maternal transmission is the main mode of transmission of hepatitis B virus, this part mainly discusses the mother HBs Ag carriers newboms still risk factors for chronic infection in active passive immunization, to further control the maternal fetal transmission of hepatitis B virus (Mother to Child Transmission, MTCT) to provide the reference. Methods: to collect the mother and children were carrying HBs Ag and Ag HBs, the mother carrying a child's health and health of mothers and their children are the mother's blood RNA was extracted by RNA reverse transcription of C DNA by RT2 Profiler PCR Array and Affymetrix Prime View Human Gene Expression Array were significant the differentially expressed genes. Results: the participation of the innate immune response of 84 key genes screening differential expression of 11 genes, including the 9, there are 2 people down. The expression can be detected by microarray gene number 20000, through the analysis of 8 types of mother to child transmission of HBV related genes, including 1 genes up-regulated and 7 genes were downregulated. Conclusion: genes involved in innate reaction differentially expressed the cell signal transduction, cell migration, angiogenesis, apoptosis, cancer and a variety of biological processes, they may play an important role in maternal fetal transmission of hepatitis B virus, need more samples to verify this result and find the possible mechanism.

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R186

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本文編號(hào)：1729456