本文選題：人乳頭瘤病毒 + 宮頸癌　； 參考：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:研究宮頸高危型人乳頭瘤病毒(high risk human papillomavirus,HR-HPV)持續(xù)感染過程中宮頸局部Th1/Th2/Th17/Treg細胞相關(guān)的8種細胞因子的變化,包括白介素-2(interleukin-2,IL-2)、IL-4、IL-6、IL-10、干擾素-γ(γ-interferon,IFN-γ)、腫瘤壞死因子(tumor necrosis factor,TNF)、IL-17A及轉(zhuǎn)化生長因子-β(transforming growth factor-β,TGF-β)。進一步分析不同HR-HPV感染亞型引起的幾種細胞因子濃度變化,對IL-6的單核苷酸多態(tài)性(single nucleotide polymorphism,SNP)進行檢測,分析多態(tài)性對HR-HPV持續(xù)感染及IL-6濃度的影響,為預(yù)防HR-HPV持續(xù)感染及宮頸病變進展提供理論依據(jù)。方法:選取2015年11月至2016年6月期間就診于天津市中心婦產(chǎn)科醫(yī)院陰道鏡門診的有HR-HPV感染史的210位已婚女性,所有研究對象均需簽署知情同意書。按照HR-HPV感染情況分為兩組,既往HR-HPV感染轉(zhuǎn)陰組及HR-HPV持續(xù)感染組各105例,持續(xù)感染組按照宮頸活檢病理進一步分為無宮頸鱗狀上皮內(nèi)病變組(non squamous intraepithelial lesion,NSIL)35例、低度宮頸上皮內(nèi)病變組(low grade squamous intraepithelial lesion,LSIL)35例、高度宮頸上皮內(nèi)病變組(high grade squamous intraepithelial lesion,HSIL)35例。采集研究對象陰道灌洗液(以下簡稱灌洗液)及宮頸脫落細胞。用流式BD CBA(cytometric bead array)及酶聯(lián)免疫吸附法(enzyme-linked immunosorbent assay,Elisa)對灌洗液中8種細胞因子水平進行檢測,提取宮頸脫落細胞中的DNA,使用巢式PCR(polymerase chain reaction)及焦磷酸測序技術(shù)對HR-HPV進行分型及IL-6兩個位點rs1800795(-174 G/C)、rs1800796(-572 C/G)的SNP檢測。應(yīng)用SPSS17.0對數(shù)據(jù)進行分析,計量資料均采用均數(shù)±標準差(??±s)表示,組間比較采用單因素方差分析,進一步的兩組比較用LSD-t法;兩組間比較使用獨立樣本t檢驗,計數(shù)資料采用卡方檢驗,P0.05為差異有統(tǒng)計學(xué)意義。結(jié)果:1.IL-2濃度在HR-HPV持續(xù)感染組低于轉(zhuǎn)陰組,且隨著病變加重濃度逐漸降低(P0.05),IL-6濃度變化恰好相反,余6種細胞因子水平在組間差異無統(tǒng)計學(xué)意義。2.轉(zhuǎn)陰組及持續(xù)感染組中各細胞因子濃度均與絕經(jīng)狀態(tài)無相關(guān)性。3.HR-HPV持續(xù)感染者中最常見的型別為HPV16(50.48%)。4.與其他高危亞型相比,HPV16感染引起的宮頸局部細胞因子變化并無差異。5.IL-6 rs1800795(-174G/C)、rs1800796(-572 C/G)基因型及等位基因頻率在HR-HPV持續(xù)感染組與轉(zhuǎn)陰組比較無差異。6.IL-6濃度與rs1800795(-174G/C)、rs1800796(-572 C/G)多態(tài)性無相關(guān)性。結(jié)論:1.用流式BD CBA方法進行陰道局部灌洗液中細胞因子的檢測為研究HR-HPV持續(xù)感染過程中宮頸局部免疫微環(huán)境改變提供了新的思路。2.IL-2、IL-6在HR-HPV持續(xù)感染過程中有重要作用,IL-2隨病變程度加重濃度逐漸降低,IL-6隨病變加重濃度逐漸升高,HR-HPV持續(xù)感染過程中存在Th1/Th2漂移現(xiàn)象。3.HR-HPV持續(xù)感染最常見的亞型為HPV16。但HPV16與其他高危亞型感染相比引起宮頸局部8種細胞因子水平的改變無差異。4.IL-6 SNP的研究為從遺傳學(xué)角度分析HR-HPV持續(xù)感染的原因提供了思路,發(fā)現(xiàn)影響HR-HPV持續(xù)感染的多態(tài)性位點會為預(yù)防HR-HPV持續(xù)感染及病變進展提供新的理論依據(jù)。
[Abstract]:Objective: To study the changes of 8 cytokines related to cervical local Th1/Th2/Th17/Treg cells during the continuous infection of cervical high-risk human papillomavirus (high risk human papillomavirus, HR-HPV), including interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon gamma, tumor necrosis factor. Factor, TNF), IL-17A and transforming growth factor - beta (transforming growth factor- beta, TGF- beta). Further analysis of the changes in the concentration of several cytokines caused by different HR-HPV infection subtypes, and detect the single nucleotide polymorphisms of IL-6 (single nucleotide polymorphism), and analyze the effect of polymorphism on persistent infection and concentration of HR-HPV. To provide a theoretical basis for preventing HR-HPV persistent infection and progression of cervical lesions. Methods: 210 married women who had a history of HR-HPV infection in the colposcopy clinic of Tianjin Central Obstetrics and Gynecology Hospital from November 2015 to June 2016 were selected. All the subjects needed to sign informed consent. According to the HR-HPV infection, two groups were divided into H. The R-HPV infection group and the HR-HPV continuous infection group were 105, and the continuous infection group was further divided into 35 cases without cervical squamous intraepithelial lesion (non squamous intraepithelial lesion, NSIL), 35 cases of low cervical intraepithelial lesion (low grade squamous intraepithelial lesion), and high cervical intraepithelial disease. 35 cases of high grade squamous intraepithelial lesion (HSIL) were used to collect the vaginal lavage fluid (hereinafter referred to as the lavage solution) and the cervical exfoliative cells. The level of 8 cytokines in the lavage liquid was detected by flow BD CBA (cytometric bead array) and enzyme linked immunosorbent assay. DNA in the exfoliated cells of the cervix, using polymerase chain reaction and pyrosequencing technology to classify HR-HPV and IL-6 two loci rs1800795 (-174 G/C), rs1800796 (-572). The two groups were compared with the LSD-t method; the two groups were compared with the independent sample t test, the count data were taken by chi square test, and the difference of P0.05 was statistically significant. Results: the concentration of 1.IL-2 in HR-HPV continuous infection group was lower than that in the negative group, and with the increasing concentration of the lesions (P0.05), the IL-6 concentration changed exactly the opposite, the remaining 6 species were the opposite. There was no significant difference in the level of cytokines between the groups and the.2. negative group and the persistent infection group. The most common type of.3.HR-HPV persistent infection in the patients with menopause was the most common type of HPV16 (50.48%).4., compared with other high-risk subtypes, the changes of cervical local cytokines caused by HPV16 infection did not differ from.5.IL-6 rs. 1800795 (-174G/C), rs1800796 (-572 C/G) genotype and allele frequency had no difference between.6.IL-6 concentration and rs1800795 (-174G/C), rs1800796 (-572 C/G) polymorphism in the HR-HPV continuous infection group and the negative group. Conclusion: 1. the detection of cytokine in the local lavage liquid of the vaginal canal was carried out by the flow BD method. The local immune microenvironment changes during the dyeing process provide a new idea.2.IL-2. IL-6 plays an important role in the continuous infection process of HR-HPV. The concentration of IL-2 gradually decreases with the severity of the lesion, IL-6 increases with the aggravation of the lesion, and the most common subtype of Th1/Th2 drift in.3.HR-HPV continues to exist during the continuous HR-HPV infection. The study of changes in the level of 8 cytokine levels of the cervix caused by HPV16. but HPV16 compared with other high-risk subtypes of.4.IL-6 SNP provides a way of thinking to analyze the causes of persistent HR-HPV infection from the genetic perspective. It is found that polymorphic loci affecting the continuous infection of HR-HPV will provide the prevention of HR-HPV persistent infection and the progression of the disease. A new theoretical basis.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.33

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