本文選題：人乳頭狀瘤病毒　切入點(diǎn)：宮頸癌　出處：《新疆醫(yī)科大學(xué)》2015年博士論文

【摘要】：目的:在維族、漢族HPV篩檢出陽(yáng)性的女性人群中分別檢測(cè)血清中IL-2及IL-6、IL-10、IFN-γ、人乳頭狀瘤病毒(HPV)L1抗體,同時(shí)檢測(cè)HPVLI殼蛋白在組織中和TCT保存液中的表達(dá);組織中HPV16DNA L1、E6、E7基因的載量,HPV16L1、HPVE6、E7蛋白、HPV E6/E7mRNA在宮頸病變組織中的表達(dá)情況,評(píng)價(jià)這些檢測(cè)在宮頸病變篩查及宮頸癌風(fēng)險(xiǎn)預(yù)警中的作用,能為用于臨床提供一些理論依據(jù),探索維族婦女有別于漢族婦女宮頸病變的發(fā)病原因及臨床相關(guān)指標(biāo)。方法:收集2013年8月~2015年6月新疆自治區(qū)人民醫(yī)院婦科和門(mén)診都自己愿意接受宮頸癌機(jī)會(huì)性篩查維吾爾族婦女,分別利用HC-2、HPV DNA、HPV分型技術(shù)確定HPV的型別及感染情況,分為宮頸炎組、CINI組、CINII-III組、宮頸癌組,利用酶聯(lián)免疫吸附法(ELISA)、免疫組化法分別測(cè)定患者血清、宮頸組織中IL-2及IL-6、IL-10、IFN-γ的水平;對(duì)HPV結(jié)果陽(yáng)性的其中197例標(biāo)本分別用免疫細(xì)胞化學(xué)法、免疫組化法檢測(cè)HPV L1殼蛋白在宮頸脫落細(xì)胞中、宮頸組織中的表達(dá),利用RT-PCR技術(shù)檢測(cè)HPV16DNA L1、E6、E7基因、western-blot技術(shù)檢測(cè)HPV16L1、E6、E7蛋白水平,同時(shí)利用酶聯(lián)免疫吸附法(ELISA)測(cè)定該197份標(biāo)本的患者血清中HPV16L1抗體的表達(dá);對(duì)宮頸病變患者采用APTIMA方法進(jìn)行高危型HPV E6/E7 mRNA檢測(cè),以宮頸組織病理學(xué)結(jié)果為標(biāo)準(zhǔn)。結(jié)果:IFN-γ在宮頸組織中的表達(dá)均隨宮頸病變級(jí)別的增加而減少,IL-10的表達(dá)均隨著宮頸病變級(jí)別的加重而增加,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。各個(gè)宮頸病變級(jí)別的患者血清中IL-2、IFN-γ的水平均隨著宮頸病變嚴(yán)重程度的增加而減少,IL-6、IL-10的水平均隨著宮頸病變級(jí)別的加重而增加,差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。分層后維吾爾族婦女與漢族婦女之間,IL-6、IL-10的水平比較無(wú)統(tǒng)計(jì)學(xué)差異(均P0.05)。HPV L1殼蛋白在組織中和脫落細(xì)胞液中陽(yáng)性表達(dá)率隨著宮頸病變級(jí)別的增加呈下降的趨勢(shì),差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。血清中HPV16L1抗體隨著宮頸病變級(jí)別的加重,抗體水平升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。維吾爾族婦女與漢族婦女之間比較無(wú)統(tǒng)計(jì)學(xué)差異(均P0.05)。宮頸組織中隨著宮頸病變級(jí)別的加重HPV16E6、E7蛋白表達(dá)增加,差異有統(tǒng)計(jì)學(xué)意義(P0.05);宮頸組織中HPVE6/E7mRNA隨著宮頸病變嚴(yán)重程度的增加而增加,差異有統(tǒng)計(jì)學(xué)意義(P0.05),而且HPVE7、E6蛋白和HPVE6/E7mRNA表達(dá)具有相關(guān)性,差異有統(tǒng)計(jì)學(xué)意義。在兩個(gè)民族之間不同病理級(jí)別中進(jìn)行比較,HPVE6/E7mRNA差異無(wú)統(tǒng)計(jì)學(xué)意義。HPV E6/E7 mRNA檢測(cè)能預(yù)測(cè)高級(jí)別宮頸病變,陰性預(yù)測(cè)值=81.01%;陽(yáng)性預(yù)測(cè)值=72.88%;準(zhǔn)確性=76.14%。病理類(lèi)型分層漢族和維吾爾族HPV16E7DNA載量的差別均無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論:宮頸病變和子宮頸癌的最主要致病因素是HPV持續(xù)感染;各組患者血清中IL-2、IFN-γ的水平均隨著宮頸病變嚴(yán)重程度的增加而減少,IL-6、IL-10的水平均隨著宮頸病變級(jí)別的加重而增加,IFN-γ在宮頸組織中的表達(dá)隨著宮頸病變嚴(yán)重程度的增加而減少,IL-10的表達(dá)均隨著宮頸病變級(jí)別的加重而增加;HPV L1殼蛋白的陽(yáng)性表達(dá)隨著宮頸病變的級(jí)別增加而下降,維族漢族之間相等級(jí)別宮頸病變之間的表達(dá)無(wú)差異;HPV16E6、E7蛋白、HPVE6/E7 mRNA在組織中的表達(dá)隨著宮頸病變級(jí)別的加重表達(dá)增加,HPVL1蛋白檢測(cè)及HPVE6/E7 mRNA有望成為預(yù)測(cè)維吾爾族宮頸病變嚴(yán)重程度的重要生物學(xué)標(biāo)志物。
[Abstract]:Objective: in the Uygur, Han HPV screening were detected positive women in IL-2 and IL-6, IL-10 in serum, IFN- gamma, human papilloma virus (HPV) L1 antibody, simultaneous detection of HPVLI protein in the tissue and shell TCT to save the expression in the liquid; HPV16DNA in L1, E6, load, E7 gene HPV16L1, HPVE6, E7 protein, expression of HPV E6/E7mRNA in cervical lesions, evaluate the effects of these test in screening of cervical lesions and cervical cancer risk prediction, can provide some theoretical basis for exploration for clinical, Uighur women is different from the Han nationality women in etiology of cervical lesions and clinical indicators. Methods: from August 2013 June ~2015 in Xinjiang Autonomous Region People's hospital gynecological outpatient and are themselves willing to accept the opportunistic screening for cervical cancer in Uygur women, respectively by HC-2, HPV DNA, HPV genotyping technology to determine the type and infection of HPV, Divided into CINI group, cervicitis group, CINII-III group and cervical cancer group, using enzyme-linked immunosorbent assay (ELISA), the serum was measured by immunohistochemistry method respectively, IL-10 IL-2 and IL-6 in cervical tissue, IFN- gamma level; immunocytochemistry were used to HPV positive results from 197 cases. Immunohistochemical detection of HPV L1 capsid protein in cervical exfoliated cells, expression in cervical tissue, detected by HPV16DNA L1, RT-PCR E6, E7 gene, HPV16L1 detection, Western-blot E6, E7 protein level by enzyme-linked immunosorbent assay (ELISA) expression of HPV16L1 antibody of the 197 specimens of serum determination of the detection of high-risk HPV E6/E7; mRNA APTIMA method on patients with cervical lesions in the cervical tissue, the pathological results. Results: IFN- expression in cervical tissues were increased with the level of cervical lesions and decrease the expression of IL-10 was Increases with the level of cervical lesions increased, the differences were statistically significant (P0.05). The IL-2 level in serum of patients with cervical lesions, IFN- gamma levels were decreased with the increase of the severity of cervical lesions and IL-6, IL-10 levels were increased with the increased level of cervical lesions, the differences were statistically significant (P0.05). IL-6, after stratification in Uigur and Han women, no significant differences between the levels of IL-10 (P0.05).HPV L1 protein positive cells in the liquid shedding rate decreased with the level of cervical lesions in the tissue and, the differences were statistically significant (P0.05). The serum HPV16L1 antibody with aggravation of cervical lesions the level of antibody level increased, the difference was statistically significant (P0.05). Between Uigur and Han women had no significant difference (P0.05) in cervical tissue with. HPV16E6 increased the level of cervical lesions, the expression of E7 protein increased, the difference was statistically significant (P0.05); HPVE6/E7mRNA in cervical tissue increased with the severity of cervical lesions, the difference was statistically significant (P0.05), and HPVE7, E6 protein and HPVE6/E7mRNA expression has correlation, the difference was statistically significant. Compared in different pathological the level of HPVE6/E7mRNA between the two groups, there was no significant difference in.HPV E6/E7 mRNA can predict the detection of high grade cervical lesions, negative predictive value, positive predictive value of =81.01%; =72.88% = 76.14%.; the accuracy of pathological types of layered Han and Uygur HPV16E7DNA load difference was not statistically significant. Conclusion: the main pathogenesis of cervical lesions and cervical cancer is HPV persistent infection; serum IL-2 groups, IFN- gamma levels were reduced with the increase of the severity of cervical lesions and IL-6, IL-1 0 levels were increased with the aggravation of cervical lesions and IFN- expression in cervical tissues decreased with the severity of cervical lesions, the expression of IL-10 was increased with increasing the level of cervical lesions; the positive expression of HPV L1 capsid protein decreased with the level of cervical lesions increased, no difference between the expression of between Uygur and Han people in equal levels of cervical lesions; HPV16E6, E7 protein, the expression of HPVE6/E7 mRNA in tissues with the level of cervical lesions increased increased expression of HPVL1 protein detection and HPVE6/E7 mRNA is expected to become an important biological prediction of Uygur cervical lesion severity markers.

【學(xué)位授予單位】：新疆醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R737.33

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