结核分枝杆菌DNA疫苗对小鼠结核病免疫治疗作用的实验研究

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目的探讨结核分枝杆菌DNA疫苗pcD85B、pcDMPT64以及小鼠白细胞介素12(IL-12)真核表达质粒psIL12对结核分枝杆菌感染的疗效与机制。方法将结核分枝杆菌H37Rv感染的C57BL/J6小鼠100只随机分成生理盐水对照组、pcDNA3.1对照组,psIL12治疗组,pcD85B、pcDMPT64、pcD85B+pcDMPT64、pcD85B+psIL12DNA疫苗治疗组。感染4周后分别给予生理盐水、空质粒、psIL-12及DNA疫苗,第1次治疗后2个月处死小鼠,检测器官荷菌量、脾淋巴细胞特异性γ干扰素(IFN-γ)、白细胞介素4(IL4)、肿瘤坏死因子-α(TNF-α)的分泌水平,并于第1次治疗后2个月、5个月观察小鼠肺、脾组织病理改变情况。结果pcD85B治疗组肺组织荷菌量(lg-1CFU/g)为6.99±0.40,比生理盐水对照组(8.15±0.37)、pCDNA3.1对照组(8.19±0.29)显著降低(P<0.01);脾组织荷菌量(lg-1CFU/g,x±s)为5.17±0.33,比生理盐水对照组(5.76±0.16)及空质粒对照组(5.88±0.21)显著降低(P<0.05)。psIL12治疗组的肺(7.41±0.50)、脾(5.31±0.21)荷菌量比对照组显著降低(P<0.05);pcD85B+psIL12治疗组肺、脾荷菌量与pcD85B组比较差别无统计学意义。pcD85B组脾淋巴细胞IFN-γ、TNFα水平比对照组显著升高(P<0.05),各组间IL4水平差异无统计学意义。生理盐水对照组、pCDNA3.1对照组肺组织? Objective To investigate the efficacy and mechanism of Mycobacterium tuberculosis DNA vaccine pcD85B, pcDMPT64 and murine interleukin-12 (IL-12) eukaryotic expression plasmid psIL12 on Mycobacterium tuberculosis infection. Methods 100 C57BL / J6 mice infected with Mycobacterium tuberculosis H37Rv were randomly divided into saline control group, pcDNA3.1 control group, psIL12 treatment group, pcD85B, pcDMPT64, pcD85B + pcDMPT64 and pcD85B + psIL12 DNA vaccine treatment groups. After 4 weeks of infection, the mice were sacrificed 2 weeks after the first treatment with physiological saline, empty plasmid, psIL-12 and DNA vaccine respectively. The numbers of organs, spleen lymphocyte specific IFN-γ, , IL-4 and TNF-α were measured. Pathological changes of lung and spleen were observed at 2 and 5 months after the first treatment. Results Compared with saline control group (8.15 ± 0.37) and pCDNA3.1 control group (8.19 ± 0.29), pcD85B treatment group showed a significant decrease in drug load (lg-1CFU / g) The spleen load (lg-1CFU / g, x ± s) was 5.17 ± 0.33, which was significantly lower than that of saline control group (5.76 ± 0.16) and empty plasmid control group (5.88 ± 0.21) (P <0.05). Psil12 treatment group lung (7.41 ± 0.50), spleen (5.31 ± 0.21) bacterial load than the control group was significantly lower (P <0.05); pcD85B + psIL12 treatment group lung and spleen load compared with pcD85B group no statistical difference significance. The levels of IFN-γ and TNFα in splenic lymphocytes of pcD85B group were significantly higher than those in control group (P <0.05). There was no significant difference in the level of IL4 between groups. Saline control group, pCDNA3.1 control group lung tissue?
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