中文摘要：

目的：检测不同耐药的结核杆菌临床分离株原核类泛素蛋白-蛋白酶体系统（以下简称：Pup-蛋白酶体系统）相关的Pup、Dop、PafA、Mpa基因的表达水平,探讨研究结核杆菌Pup-蛋白酶体系统与新疆地区广泛流行的耐药结核杆菌临床分离株耐药性的相关性。方法：以培养对数生长期的新疆地区广泛流行的耐药结核杆菌临床分离株为研究对象,分别提取结核杆菌临床分离的药物敏感菌株、单纯耐异烟肼的结核杆菌临床分离株（INH-MTB）、单纯耐利福平的结核杆菌临床分离株（RFP-MTB）、单纯耐链霉素的结核杆菌临床分离株（SM-MTB）、单纯耐乙胺丁醇的结核杆菌临床分离株（EB-MTB）、耐多药结核杆菌临床分离株（MDR）等各组菌株的总RNA,经纯度鉴定后,利用SYBR GreenⅠ实时荧光定量PCR方法,检测各组结核杆菌菌株的Pup、Dop、PafA、Mpa基因的表达水平,分析各组耐药结核杆菌临床分离株Pup-蛋白酶体系统相关的Pup、Dop、PafA、Mpa基因的表达与新疆地区广泛流行的耐药结核杆菌临床分离株耐药性的相关性。结果：与药物敏感菌株相比,Pup、Mpa基因在单一耐药菌株和耐多药菌株中表达有不同程度的下调,Dop、PafA基因在单一耐药菌株和耐多药菌株中表达有不同程度的上调,差异有统计学意义（P〈0.05）。与MDR相比,Pup、Dop、Mpa基因在单一耐药菌株中表达有不同程度的上调,PafA基因在单一耐药菌株中表达有不同程度的下调,差异有统计学意义（P〈0.05）。结论：在结核杆菌临床分离的药物敏感菌株、INH-MTB组、RFP-MTB组、SM-MTB组、EB-MTB组和MDR组中,结核杆菌Pup、Dop、PafA、Mpa基因的表达差异,与新疆地区广泛流行的耐药结核杆菌临床分离株耐药性有相关性。

英文摘要：

Objective： To study the correlation different drug-resistant mycobacterium tuberculosis clinical isolates of prokaryotic ubiquitin-like protein（ Pup）-proteasome of Pup,Dop,PafA,Mpa gene expression level and mycobacterium tuberculosis Pup- proteasome system with Xinjiang region widely popular drug-resistant mycobacterium tuberculosis in clinical isolates resistance. Methods：Total RNA of Mtb was extracted from cultured Mtb during the logarithmic phase in drug-susceptible strains in Xinjiang region,the clinical strains drug sensitive to INH,RFP,SM and EB respectively,and multidrug-resistant（ MDR） strains. And then the purity of total RNA was identified. The expressing of Pup-proteasome relevant gene（ Pup,Dop,Mpa,PafA） were quantified using SYBR GreenⅠqRT-PCR which aimed at finding the correlation between Mtb Pup-proteasome system and drug resistance of Mtb clinical isolates widespread in Xingjiang region by analyzing the expression of Pup,Dop,PafA,Mpa gene among different isolates. Results： Compared with the drug-senstive clinical isolates,mRNA expression level of Pup,Mpa gene was down-regulated in resistant M. tuberculosis clinical isolates INH（ INH-MTB）,RFP（ RFP-MTB）,SM（ SM-MTB） and EB（ EB-MTB）,mRNA expression levels of genes in Dop and PafA was higher in resistant M. tuberculosis clinical isolates,the difference was statistically significant（ P〈0. 05）. Compared with MDR strain,the expression of Pup,Dop,Mpa gene were up-regulated different in the resistant M. tuberculosis clinical isolates isolates,the expression of PafA gene was down-regulated different,the difference was statistically significant（ P〈0. 05）. Conclusion： The differentially expressed gene of Pup、Dop、PafA、Mpa gene in sensitive strains,INH-MTB,RFP-MTB,SM-MTB,EB-MTB and MDR strains. The Mycobacterium tuberculosis Pup- proteasome system. Therefore,the Pup-proteasome system have association with the drug resistance of Mtb strains widespread in Xinjiang region.