本文選題：人乳頭瘤病毒 + 尖銳濕疣��； 參考：《中國協(xié)和醫(yī)科大學》2010年博士論文

【摘要】： 【背景】人乳頭瘤病毒是一廣泛存在的病毒,可以引起良性(低風險型)和惡性的(高風險型)皮膚或粘膜的皮損,但關于人乳頭瘤病毒的致病機制還不清楚。人乳頭瘤病毒感染可能和朗格漢斯細胞,T淋巴細胞,病毒本身等因素有關,此外,還可能與部分患者的某些基因出現(xiàn)甲基化和細胞因子的變化有關。疣狀表皮發(fā)育不良患者出現(xiàn)人乳頭瘤病毒易感可能與EVER1/2基因的突變有關。 【目的】本論文通過研究尖銳濕疣患者DNA甲基化和疣狀表皮發(fā)育不良中朗格漢斯細胞和細胞因子的變化,探討人乳頭瘤病毒相關性皮膚病的發(fā)病機制。 【方法】 從基因角度研究尖銳濕疣的發(fā)病和DNA甲基化之間的關系,采用甲基化特異性聚合酶鏈式反應,對51例尖銳濕疣患者及47例正常對照進行實驗,觀察對人乳頭瘤病毒易感的EVER1基因甲基化的陽性率,對尖銳濕疣和EVER1基因甲基化之間的關系進行研究,以探討尖銳濕疣的發(fā)病機制。 采用免疫組化方法檢測疣狀表皮發(fā)育不良病人中朗格漢斯細胞和細胞因子的表達情況,以研究細胞因子在其發(fā)病中的作用。選取10例疣狀表皮發(fā)育不良病人的皮損,對其表皮中朗格漢斯細胞的表面標記分子CD1a和CD83,及與免疫反應相關的IL-10,IL-23和CD86三種細胞因子進行免疫組化染色并觀察其表達,同時以10例正常人的眼皮標本作對照。 【結果】 尖銳濕疣組中甲基化陽性率為13.73%(7／51),部分甲基化率為17.65%(9／51),非甲基化率為68.62%(35／51),總的甲基化陽性率為31.38%。正常對照組的甲基化陽性率8.51%(4／47),部分甲基化率為2.13%(1／47),非甲基化率為89.36%(42／47),總的甲基化陽性率為10.64%。兩組比較有顯著性差異(p0.05)。 在疣狀表皮發(fā)育不良的所有組織中均可見到CD1a陽性表達的朗格漢斯細胞,未見CD83陽性表達的朗格漢斯細胞,且CD1a陽性的朗格漢斯細胞的計數(shù)在EV組較正常組相比明顯降低且分布不均勻。疣狀表皮發(fā)育不良組中IL-10,IL-23和CD86三種細胞因子的表達為陽性,而正常組有1例IL-10陽性,其余均為陰性；病例組中三種細胞因子的評分為3-6分,而正常組除了IL-10中的1例為3分,其余均為0分；病例組中三種細胞因子的陽性率為(++)-(+++),而正常組中除了IL-10中的1例為(++),其余均為(-),疣狀表皮發(fā)育不良組三種細胞因子表達陽性率明顯高于正常組。 【結論】 本研究結果顯示尖銳濕疣患者甲基化發(fā)生率為31.38%,高于正常對照組(p0.05),表明尖銳濕疣的發(fā)生可能和EVER1基因啟動子區(qū)的甲基化相關。 在疣狀表皮發(fā)育不良組中CD1a陽性的朗格漢斯細胞的變化和CD83的不表達說明朗格漢斯細胞的功能可能受到抑制,使其不能轉(zhuǎn)變?yōu)槌墒鞝顟B(tài)并刺激T細胞發(fā)生免疫反應,從而造成了人乳頭瘤病毒的感染。而IL-10,IL-23和CD86的陽性表達說明疣狀表皮發(fā)育不良的發(fā)病還可能和角質(zhì)形成細胞分泌的細胞因子有關。
[Abstract]:Human papillomavirus ( HPV ) is a widely - occurring virus that can lead to benign ( low - risk ) and malignant ( high - risk ) skin or mucosal lesions , but the pathogenesis of human papillomavirus is not clear . Human papilloma virus infection may be associated with factors such as Langehan cells , T lymphocytes , virus itself , etc . In addition , methylation and changes in cytokines may be associated with some genes in some patients . The presence of human papillomavirus in patients with verrucous epidermal dysplasia may be associated with mutations in the adenovirus 1 / 2 gene .



Objective : To study the pathogenesis of human papillomavirus - related skin disease by studying the changes of cell and cytokine in DNA methylation and verrucous epidermal dysplasia in patients with Condyloma Acuminatum .



Methodology



The relationship between the pathogenesis and DNA methylation of Condyloma Acuminatum was studied from the perspective of gene . The methylation specific polymerase chain reaction was used to study 51 patients with Condyloma Acuminatum and 47 normal controls . The positive rate of methylation of HPV 1 gene susceptible to human papilloma virus was observed .



In order to investigate the role of cytokines in the pathogenesis of verrucous epidermal dysplasia , immunohistochemical staining was used to investigate the role of cytokines in the pathogenesis of verrucous epidermal dysplasia . Ten patients with verrucous epidermal dysplasia were selected to study the expression of CD1a and CD83 , IL - 10 , IL - 23 and CD83 related to immune response and to observe the expression of cytokines .



The result is not valid .



The positive rate of methylation was 13.73 % ( 7 / 51 ) , the partial methylation rate was 17.65 % ( 9 / 51 ) , the non - methylation rate was 68.62 % ( 35 / 51 ) , the total methylation rate was 31.38 % . The methylation rate of the normal control group was 8.51 % ( 4 / 47 ) , the partial methylation rate was 2.13 % ( 1 / 47 ) , the non - methylation rate was 89.36 % ( 42 / 47 ) , the total methylation rate was 10.64 % .



The positive expression of CD1a was found in all tissues of verrucous epidermal dysplasia , and the positive expression of CD1a cells was not observed . The counts of CD1a - positive cells were significantly lower in EV group than in the normal group and the distribution was not uniform . The expression of IL - 10 , IL - 23 and CD1a in patients with verrucous epidermal dysplasia was positive , while in the normal group , there were 1 case of IL - 10 positive , while the rest were negative .
The score of three cytokines in the case group was 3 - 6 , while in the normal group , one in IL - 10 was 3 and the rest was 0 .
The positive rates of three cytokines in the case group were ( ++ ) - ( ++ ) , while in the normal group , the positive rates of three cytokines were ( + ) , ( - ) and ( - ) , and the positive rates of three cytokines in the verrucous epidermal dysplasia group were significantly higher than those in the normal group .



Conclusion



The results showed that the incidence of methylation was 31.38 % in patients with Condyloma Acuminatum , which was higher than that of the normal control group ( p < 0.05 ) .



The changes of CD1a positive cells and the non - expression of CD83 in the verrucous epidermal dysplasia group suggest that the function of the cells may be inhibited so that it can not be transformed into a mature state and stimulate T cell immune response , thus causing human papillomavirus infection . The positive expression of IL - 10 , IL - 23 and CD86 suggests that the pathogenesis of verrucous epidermal dysplasia may also be related to the cytokines secreted by keratinocytes .

【學位授予單位】：中國協(xié)和醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2010
【分類號】：R752

【引證文獻】

相關期刊論文 前1條

1 駱偉雄;王天理;;普薩菲林治療尖銳濕疣臨床觀察分析[J];齊齊哈爾醫(yī)學院學報;2012年18期

，

本文編號：1897696