小鼠肺、肝、脾组织病理学变化对结核DNA疫苗保护效力的评价作用  

Evaluation of protective effectiveness of two tuberculosis DNA vaccines in relation to pathological changes in lung, liver and spleen

作　　者：徐燕杰[1] 吴雪琼[2] 韩永[2] 郑越[2] 张俊仙[2] 张灵霞[2] 史迎昌[2] 李洪敏[2] 曹立雪[2] 李忠明 

机构地区：[1]解放军总医院309临床部,北京100091 [2]北京结核病研究所 [3]上海海规生物科技有限公司

出　　处：《解放军医学杂志》2004年第12期1068-1072,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金资助课题 (编号 30 0 70 730 )

摘　　要：目的　评价结核分支杆菌MPT6 4、ESAT6DNA疫苗的保护效力和细胞因子的增强作用。方法　将BALB/C小鼠随机分为 14组 ,分别用ESAT6 (2 5 μg) +MPT6 4 (2 5 μg) (A组 ) ,ESAT6 (10 0 μg) +IFN γ(10 0 μg) (B组) ,ESAT6 (75 μg) +MPT6 4 (2 5 μg) (C组 ) ,ESAT6 (10 0 μg) +IL 12 (10 0 μg) (D组 ) ,MPT6 4 (10 0 μg) +IL 12 (10 0 μg) (E组 ) ,ESAT6 (2 5 μg) +MPT6 4 (75 μg) (F组 ) ,MPT6 4 (10 0 μg) (G组 ) ,PvaX1载体质粒 (10 0 μg) (H组) ,ESAT6 (10 0 μg) (I组 ) ,ESAT6 (10 0 μg) +MPT6 4 (10 0 μg) (J组 ) ,ESAT6 (5 0 μg) +MPT6 4 (5 0 μg) (K组) ,MPT6 4 (10 0 μg) +IFN γ(10 0 μg) (L组 ) ,卡介苗(M组) ,生理盐水 (N组 )免疫小鼠。每组各 6只小鼠免疫 8周后以结核分支杆菌H37Rv小鼠尾静脉攻击小鼠。攻击 4周后 ,观察肺、肝、脾组织的病理改变。结果　结核分支杆菌攻击后 ,肺组织病理改变为 :以渗出性反应为主的病变有N组 ,表现为肺泡壁毛细血管充血 ,肺泡腔内充满渗出液 ;以增殖性反应为主的病变为M、J组 ,表现为较多淋巴细胞、泡沫样细胞、上皮样细胞、郎罕细胞组成的结核肉芽肿 ,并可见肺泡壁组织增生增厚 ;其余均为增殖性与渗出性反应的混合性病变 (A、B、C、D、E、Objective To evaluate the protective effectiveness of MPT64 and ESAT6 DNA vaccines against M. tuberculosis. Methods BALB/c mice were randomly divided into 14 groups and subjected to following treatments respectively, i.e. immunized with. ESAT6 (25μg)+MPT64 (25μg)(A), ESAT6(100μg)+IFN-γ(100μg) (B), ESAT6 (75μg)+MPT64 (25μg)(C), ESAT6(100μg)+IL-12(100μg) (D), MPT64(100μg)+IL-12(100μg) (E), ESAT6 (25μg)+MPT64 (75μg)(F), MPT64 (100μg)(G), Pvax1 (H),ESAT6 (100μg)(I), ESAT6 (100μg)+MPT64 (100μg)(J), ESAT6 (50μg)+MPT64 (50μg)(K), MPT64(100μg)+IFN-γ(100μg)(L), BCG(M ), and saline(N). Then they were infected with M. tuberculosis H37Rv via intravenous route. The pathological changes in the lung, liver, and spleen were observed after the infection. Results Eight weeks after the inoculation, there were only alveolar exudation and capillary hyperemia in the lung lesions in the mice of group N. In the mice of group M and J, main pathological changes included tuberculous granulomas consisting of numerous lymphocytes, macrophages, epithelioid cells and Langhans giant cells, and moderate hyperplasia in alveolar walls. The lung lesions of the other groups were similar, and both hyperplasia and exudate were found (A, B, C, D, E, G, H, I, K, L). No necrosis was found in all the above groups. There were hyperemia, dense lymphocytes infiltration in the portal area, and tuberculous granuloma in the liver in all the groups. No difference was found among all the groups. The pathological changes in spleen induced hyperplasia and fusion of splenic lymph nodule. The reactions in group M and J were stronger than that of the other groups. Conclusions MPT64 and ESAT6 DNA vaccines from M.tuberculosis could enhance immunity against M. tuberculosis, either they were used in combination with different dosages or with IL-12 or IFN-γ. The vaccine used in group J showed the strongest effect in enhancing immunity, almost reaching that of combined use of BCG, IFN-γ and IL-12.

关 键 词：疫苗 DNA 抗原 分支杆菌 结核 

分 类 号：R520.1[医药卫生—内科学] R361.2[医药卫生—临床医学]