小鼠psIL-12质粒抗结核分枝杆菌感染的研究

Therapeutic effect of eukaryotic expression plasmid psIL-12 on murine infection with Mycobacterium tuberculosis

目的 观察、评价小鼠白细胞介素 12真核表达质粒psIL 12对结核分枝杆菌感染小鼠细胞因子水平的影响及疗效。方法 结核分枝杆菌H37Rv感染的C5 7BL J6小鼠随机分成生理盐水、pcDNA3.1对照组 ,psIL 12治疗组 ,每组各 6只。感染 4周后分别予以生理盐水、pcDNA3.1、psIL 12 ,第1次治疗后 8周处死检测器官活菌数 ,脏器重量指数 (WI) ,脾淋巴细胞特异性IFN γ、IL 4细胞因子分泌水平 ,并观察肺、脾组织病理改变情况。结果 psIL 12治疗组肺组织活菌数 (每mglog1 0 CFU ml)为7.4 1± 0 .5 0 ,与对照组 (8.15± 0 .37、8.19± 0 .2 9)比较显著降低 (P <0 .0 5 ) ;脾组织荷菌量 (每mglog1 0CFU ml)为 5 .31± 0 .2 1,与对照组 (5 .76± 0 16、5 .88± 0 .2 1)比较显著降低 (P <0 .0 5 )。psIL 12治疗组脾脏重量指数为 0 .5 8± 0 .0 5 ,与对照组 (1.0 2± 0 .0 8、1.10± 0 .0 2 )比较显著降低 (P <0 .0 5 )。脾淋巴细胞IFN γ(pg ml)为 4 78.0± 10 .1,与对照组 (134.5± 15 .7、12 5 .1± 8.2 )比较显著升高 (P <0 .0 5 )。各组间IL 4水平差异无显著性。对照组肺组织病理改变以变质、渗出为主 ,而psIL 12治疗组以增生改变为主。对照组与治疗组间比较脾脏病理改变不明显。结论 psIL 12真核表达质粒对小鼠结核?

Objective To study the effect of eukaryotic expression plasmid psIL-12 in mice with Mycobacterium tuberculosis . Methods C57BL/J6 mice infected with Mycobacterium tuberculosis were randomized into three groups( n =6): NS group, pcDNA3.1 group, psIL-12 group, after four weeks treatment with NS, pcDNA3.1 , psIL-12 repectively. Eight weeks later killed the mice and detected. The numbers of viable bacteria in the organs, WI and the level of IFN-γ, IL-4 of spleen lymphocytes were examined. Results In psIL-12 group, the number of viable bacteria in lung(log_ 10 CFU/ml/mg) was 7.41±0.50 and 5.31±10.21 in spleen, the WI of spleen was 0.58±0.05, and IFN-γ(pg/ml) was 478.0±10.1. There was significant difference between the control groups and the therapeutic one, but no significant difference of IL-4 level was found in all groups. The main pathologic change in lung in NS group, pcDNA3.1 group was necrosis, while in psIL-12 group there were some granulomas. Conclusion psIL-12 has therapeutic effect through increacing IFN-γ production of spleen lymphocytes and modulating the balance between T_H1 and T_H2 immune response as well as enhancing the host defence against Mycobacterium tuberculosis infection.