【摘要】：研究背景 結(jié)核病仍嚴重威脅人類健康,是單一致病菌致死率最高的疾病。目前,傳統(tǒng)的細菌學檢測方法需時較長,陽性率較低,在結(jié)核病特別是肺外結(jié)核診斷上仍然存在許多問題。耐藥結(jié)核分枝桿菌的流行以及抗結(jié)核藥物的相對落后對現(xiàn)有的治療措施提出了挑戰(zhàn)。全球唯一使用的預防結(jié)核病疫苗-卡介苗也不能有效地預防最常見的成人肺結(jié)核的發(fā)生。因此,尋求新的診斷、預防和治療方法在結(jié)核病防治工作中是十分重要的。 肝素結(jié)合血凝素(heparin-binding haemagglutinin, HBHA)是結(jié)核分枝桿菌分泌的一種黏附素,在肺外播散性結(jié)核的發(fā)生中是一種重要的毒力因素。結(jié)核分枝桿菌黏附素的研究目前主要集中于黏附素與宿主細胞相互關(guān)系及其生物學特性方面的研究,在結(jié)核病免疫診斷、治療和預防方面的應用研究剛剛起步,國內(nèi)這方面仍是空白,其它細菌黏附素的研究也很少。闡明結(jié)核分枝桿菌黏附素HBHA在結(jié)核病免疫應答中的作用,探索其在結(jié)核病診斷、預防和治療等方面的應用,對于結(jié)核病防治工作中是十分重要的。 研究目的和方法 1 擴增選擇菌株的16S rDNA序列及hbhA編碼基因的特異片段,觀察結(jié)核分枝桿菌、非結(jié)核分枝桿菌標準株、肺結(jié)核病人和肺外結(jié)核病人臨床分離株是否存在hbhA基因的缺失。 2 應用克隆表達技術(shù)及親和層析技術(shù)分別從大腸桿菌和結(jié)核分枝桿菌培養(yǎng)濾液中分離純化結(jié)核分枝桿菌黏附素HBHA蛋白,以HBHA免疫小鼠觀察抗HBHA抗體的產(chǎn)生并探討其免疫原性。 3 研究結(jié)核分枝桿菌黏附素HBHA在結(jié)核病血清學診斷中的價值,明確HBHA是否具有免疫預防和治療作用。 研究結(jié)果
[Abstract]:Background Tuberculosis is still a serious threat to human health and the highest mortality rate of single pathogen. At present, traditional bacteriological detection methods take a long time, and the positive rate is low. There are still many problems in the diagnosis of tuberculosis, especially extrapulmonary tuberculosis. The prevalence of drug-resistant Mycobacterium tuberculosis and the relative backwardness of anti-tuberculosis drugs challenge the existing treatment measures. Nor does BCG, the world's only vaccine against TB, effectively prevent the most common adult TB. Therefore, the search for new diagnosis, prevention and treatment is very important in tuberculosis prevention and treatment. Heparin-binding hemagglutinin (heparin-binding haemagglutinin, HBHA), an adhesin secreted by Mycobacterium tuberculosis, is an important virulence factor in the development of extrapulmonary disseminated tuberculosis. At present, the research of Mycobacterium tuberculosis adhesin mainly focuses on the relationship between adhesin and host cells and its biological characteristics, and the application of adhesin in the immunodiagnosis, treatment and prevention of tuberculosis has just started. Domestic this aspect is still blank, other bacterial adhesin research is also very few. To clarify the role of Mycobacterium tuberculosis adhesin HBHA in the immune response of tuberculosis and to explore its application in the diagnosis prevention and treatment of tuberculosis is very important for the prevention and treatment of tuberculosis. Objective and methods 1 to amplify the 16s rDNA sequence and the specific fragment of hbhA coding gene of the selected strain, and to observe the standard strains of Mycobacterium tuberculosis and non-tuberculous mycobacterium. Whether there is a deletion of hbhA gene in clinical isolates of pulmonary tuberculosis patients and extrapulmonary tuberculosis patients. 2Clone expression technique and affinity chromatography were used to isolate and purify Mycobacterium tuberculosis adhesin HBHA protein from Escherichia coli and Mycobacterium tuberculosis culture filtrate respectively. The production and immunogenicity of anti-HBHA antibody were observed in mice immunized with HBHA. (3) to study the value of Mycobacterium tuberculosis adhesin HBHA in the serological diagnosis of tuberculosis, and to determine whether HBHA has immunoprophylactic and therapeutic effects. Research results
【學位授予單位】：北京市結(jié)核病胸部腫瘤研究所
【學位級別】：博士
【學位授予年份】：2005
【分類號】：R378

【引證文獻】

相關(guān)博士學位論文 前1條

1 葛淑敏;非結(jié)核分枝桿菌的鑒定及胞內(nèi)分枝桿菌HBHA表達和實驗免疫研究[D];吉林農(nóng)業(yè)大學;2013年

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本文編號：2457364