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小干預(yù)RNA對人乳頭瘤病毒6bE7基因表達(dá)的干預(yù)作用

發(fā)布時間:2019-03-03 11:41
【摘要】:人類乳頭瘤病毒(Human Papilloma Virus,HPV)感染引起的傳染性皮膚粘膜疣狀增生、性傳播性疾病以及惡性腫瘤是全世界范圍內(nèi)的常見病和多發(fā)病。我國最常見的性傳播性疾病尖銳濕疣(Condyloma acuminatum,CA)即由HPV感染引起,主要是6和11型。臨床上頑固難治,復(fù)發(fā)率高。目前CA的主要治療方法有物理、藥物療法(包括手術(shù)、激光、冷凍、足葉草脂、抗病毒藥、腐蝕劑或消毒劑、抗癌藥等)和免疫療法等。物理療法和藥物局部療法對肉眼可見瘤體的療效較好,但無法消除HPV感染的亞臨床狀態(tài),很難起到根治CA的效果。因此至今仍然缺乏理想的防治手段。尋求理想的治療和預(yù)防手段是我國控制尖銳濕疣的關(guān)鍵。 最近發(fā)現(xiàn)的小干預(yù)RNA(short or small interfering RNA,siRNA)對同源mRNA的轉(zhuǎn)錄后水平的表達(dá)抑制作用使尋求有效控制尖銳濕疣等HPV感染手段的人們看到了一片曙光。長為19-23個堿基的雙鏈核甘酸通過細(xì)胞內(nèi)的RNA誘導(dǎo)的沉默復(fù)合物(RNA-induced silencing complex,RISC)有效地降解內(nèi)源mRNA,干擾了靶基因的轉(zhuǎn)錄表達(dá),這種小RNA分子即為siRNA,這種現(xiàn)象稱為RNA干預(yù)(RNA interference,RNAi)。利用這種現(xiàn)象抑制某些特定基因表達(dá)來作為研究基因功能或阻斷感染病原體復(fù)制的手段即小RNA干預(yù)技術(shù)。 本研究將尖銳濕疣主要病原體HPV6b型的早期基因E7作為靶基因,研究其同源siRNA(包括雙鏈siRNA和shRNA表達(dá)質(zhì)粒)在體外實驗和動物實驗中對HPV6bE7表達(dá)的抑制作用以及對HPV感染的阻斷作用,有利于促進(jìn)RNA干預(yù)技術(shù)在尖銳濕疣等HPV感染相關(guān)疾病治療中的應(yīng)用。
[Abstract]:Verrucous hyperplasia of infectious skin mucosa caused by human papillomavirus (Human Papilloma Virus,HPV) infection, sexually transmitted diseases and malignant tumors are common and frequently occurring diseases all over the world. Condyloma acuminatum (Condyloma acuminatum,CA), the most common sexually transmitted disease in China, is caused by HPV infection, mainly 6 and 11 types. Clinically, stubborn and difficult to treat, the recurrence rate is high. At present, the main therapeutic methods of CA include physical, drug therapy (including surgery, laser, freezing, foot leaf fat, antiviral drugs, corrosion agents or disinfectants, anti-cancer drugs, etc.) and immunotherapy. Physiotherapy and local drug therapy have a good effect on visible tumors, but can not eliminate the subclinical state of HPV infection, so it is difficult to cure CA. Therefore, there is still a lack of ideal means of prevention and control. Seeking ideal treatment and prevention means is the key to control condyloma acuminatum in our country. The inhibition of the expression of homologous mRNA at the post-transcriptional level by the recently discovered small intervention RNA (short or small interfering RNA,siRNA provides a dawn for people seeking to effectively control HPV infection such as condyloma acuminatum. RNA-induced silencing complex (RNA-induced silencing complex,RISC) effectively degrades endogenous mRNA, a small RNA molecule known as siRNA, which interferes with the transcriptional expression of the target gene through a 23-base-long, double-stranded ribonucleic acid complex (RNA-induced silencing complex,RISC). This phenomenon is called RNA intervention (RNA interference,RNAi). This phenomenon is used to inhibit the expression of certain genes as a means of studying gene function or blocking the replication of infectious pathogens, that is, small RNA intervention technology. In this study, the early gene E7 of HPV6b, the main pathogen of condyloma acuminatum, was used as the target gene. To study the inhibitory effect of homologous siRNA (including double-stranded siRNA and shRNA expression plasmids) on the expression of HPV6bE7 and the blocking effect on HPV infection in vitro and in animal experiments. It is helpful to promote the application of RNA intervention technique in the treatment of HPV infection-related diseases such as condyloma acuminatum.
【學(xué)位授予單位】:浙江大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2006
【分類號】:R752;R373

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 韓志敏;人毛乳頭細(xì)胞中P16基因的檢測及意義[D];河北醫(yī)科大學(xué);2012年

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本文編號:2433664

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