DNA疫苗对感染结核分枝杆菌耐药株小鼠治疗效果的病理学评价  

Histopathological evaluation of DNA vaccines on mice infected with multi-drug-resistant Mycobacterium tuberculosis

作　　者：白雪娟[1] 李宁[1] 余琦[1] 梁艳[2] 刘成龙[1] 张俊仙[2] 阳幼荣[2] 吴雪琼[2] 

机构地区：[1]解放军第309医院病理科,北京100091 [2]解放军第309医院全军结核病研究所,北京100091

出　　处：《中华临床医师杂志（电子版）》2011年第1期60-64,共5页Chinese Journal of Clinicians(Electronic Edition)

基　　金：国家重大传染病防治科技重大专项基金资助项目(2008ZX10003-013-02)

摘　　要：目的观察HSP65DNA、Ag85ADNA、Ag85ADNA联合利福平、Ag85A/ESAT-6嵌合DNA、Ag85A/ESAT-6嵌合DNA联合利福平对感染结核分枝杆菌耐药株小鼠治疗后的肺、肝、脾脏病理组织学变化,研究和评价该DNA疫苗治疗效果。方法将用结核分枝杆菌高耐利福平低耐异烟肼临床分离株HB361尾静脉注射17～19g的6～8周龄雌性BALB/c小鼠随机分为8组,每组10只。感染后3d开始,分别用生理盐水、pVAX1空载体、利福平、HSP65DNA、Ag85ADNA、Ag85ADNA联合利福平、Ag85A/ESAT-6嵌合DNA、Ag85A/ESAT-6嵌合DNA联合利福平治疗60d。治疗结束后3周,分别取肺、肝、脾脏组织观察病理改变,抗酸染色计数脾脏残余菌量。结果生理盐水组、pVAX1空载体组及利福平组小鼠肺、肝、脾脏组织病变严重,范围广泛,各DNA疫苗治疗组小鼠的肺、肝、脾脏组织病变得到不同程度改善,以Ag85ADNA、Ag85ADNA联合利福平组最为显著,该组小鼠脾脏组织中残余菌数也最少。结论根据小鼠肺、肝、脾脏组织病理学指标变化,能够客观且有效地评价DNA疫苗对结核小鼠的治疗效果,结果表明Ag85ADNA疫苗治疗结核分枝杆菌耐药株感染小鼠效果最优。Objective By observing the histopathological changes in lung,liver and spleen of mice,to study the therapeutic effects of DNA vaccines （HSP60 DNA,Ag85A DNA,Ag85A DNA combined with rifampin,chimeric Ag85A/ESAT-6,chimeric Ag85A/ESAT-6 combined with rifampin） in the mouse model of multi-drug resistant （MDR） Mycobacterium tuberculosis infection.Methods Pathogen-free female BALB/c mice of 6-8 weeks of age were purchased.80 BALB/c mice were infected with strain HB361 by intratail-vein injection HB361,which was resistant to high level of RFP,and low level of isoniazid （INH）,and then were divided into 8 groups.After 3 days,the mice were treated by saline,vector pVAX1,rifampin,HSP60 DNA,Ag85A DNA,Ag85A DNA combined with rifampin,chimeric Ag85A/ESAT-6,chimeric Ag85A/ESAT-6 combined with rifampin for 60 days,respectively.The mice were killed after 3 weeks＇ treatment.We observed the lung,liver and spleen pathological changes and counted the residual TB in spleen by acid-fast staining.Results The pathological condition of lung,liver and spleen in mice treated by DNA vaccine were better than the control groups,especially the Ag85A DNA group and Ag85A DNA combined with rifampin group.Also the residual TB of the Ag85A DNA group and Ag85A DNA combined with rifampin group were least in spleen.Conclusions We can evaluate the therapeutic effects of DNA vaccine objectively and accurately according to the histopathological changes in lung,liver and spleen.And the results show that Ag85A DNA vaccine could be an effective agent to therapy the mouse infected by MDR-TB.

关 键 词：分枝杆菌 结核 结核 抗多种药物性 疫苗 DNA 病理学 

分 类 号：R52[医药卫生—内科学]