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目的比较颗粒溶素/白介素-12重组耻垢分枝杆菌(rMS)和微卡作为免疫治疗佐剂在鼠结核病治疗中的效果及机制。方法结核分枝杆菌H37Rv感染Balb/c小鼠4周后,分别用生理盐水、耻垢分枝杆菌(MS)、rMS、INH+PZA,rMS+INH+PZA、微卡+INH+PZA治疗6次,于第1次治疗后3个月处死小鼠,检测器官荷菌量、血清IL-12和IFN-γ分泌水平和肺、脾组织中颗粒溶素表达及观察小鼠肺、脾组织病理改变情况。结果rMS+INH+PZA器官荷菌量明显低于微卡+INH+PZA、rMS和INH+PZA药物组;血清IL-12水平rMS+INH+PZA和单纯rMS组明显高于微卡+INH+PZA和INH+PZA组;IFN-γ分泌水平rMS+INH+PZA、单纯rMS组和微卡+INH+PZA明显高于单纯的药物组;用免疫组化检测到单纯rMS组和rMS+INH+PZA组在肺脾组织中颗粒溶素的表达;rMS+INH+PZA、微卡+INH+PZA、单纯rMS组和INH+PZA组肺组织病变轻且局限,生理盐水组肺组织病理改变以渗出为主,病变广泛,正常肺泡结构被破坏。结论rMS和微卡对小鼠结核病有一定免疫治疗作用,rMS通过增强宿主Th1型免疫应答和GLS的抗菌活性有关,而微卡主要通过调节免疫应答发挥作用;rMS对临床常用的抗结核药协同作用优于微卡,为结核病的综合治疗打下实验基础。
Objective To compare the effect and mechanism of granisellin / interleukin-12 (recombinant) M. smegmatis (rMS) and micro-card as immunotherapy adjuvant in the treatment of murine tuberculosis. Methods Balb / c mice infected with Mycobacterium tuberculosis H37Rv were treated with saline, Mycobacterium smegmatis (MS), rMS, INH + PZA, rMS + INH + PZA, The mice were sacrificed 3 months after the first treatment. The organism load, the level of IL-12 and IFN-γ in sera and the expression of granulysin in lung and spleen were detected and the pathological changes of lung and spleen were observed Change the situation. Results The amount of bacterial load in rMS + INH + PZA organs was significantly lower than that in micro-card + INH + PZA, rMS and INH + PZA groups. The level of IL-12 in rMS + INH + PZA and rMS group was significantly higher than that in microarray + INH + PZA group and INH + PZA group. The levels of IFN-γ secretion rMS + INH + PZA, rMS group and micro-card + INH + PZA group were significantly higher than those of pure drug group. The expression of granulysin in PZA group was lower than that in control group. The pathological changes of lung tissue in rMS + INH + PZA, micro-card + INH + PZA, simple rMS group and INH + PZA group were mild and limited. Excessive, extensive lesions, normal alveolar structure is destroyed. Conclusion rMS and micro-card have a certain immunotherapy effect on tuberculosis in mice. RMS is related to the anti-bacterial activity of GLS by enhancing the host Th1-type immune response, while micro-card mainly plays an important role in the regulation of immune response. RMS synergies with commonly used clinical anti-tuberculosis drugs The effect is better than the micro-card, lay the experimental foundation for the comprehensive treatment of tuberculosis.