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目的探讨iclmRNA特异性10-23脱氧核酶(deoxyribozyme,DRz)对结核分枝杆菌(Mycobacterium tuberculosis,Mtb)在小鼠体内感染的影响,及其单独或与异烟肼(isoniazidum,INH)联合应用治疗小鼠结核病的效果。方法分别用DZ4、INH、INH+DZ4-S或INH+DZ4对Mtb进行预处理,再用上述经过预处理的Mtb感染BALB/c小鼠,一定时间后进行小鼠肺组织Mtb培养及病理学改变观察。利用DZ4-FITC溶液对BALB/c小鼠进行滴鼻处理,检测滴鼻途径给药的效果。采用尾静脉注射法建立小鼠结核病模型,将模型小鼠随机分为5组(n=10),分别给予生理盐水、DZ4、INH、INH+DZ4、INH+DZ4-polyG治疗,于治疗完成2周后进行小鼠肺组织Mtb荷菌量检测和病理学改变观察。结果Mtb感染后2周,各组小鼠的肺组织荷菌量均无显著性差异(P>0.05)。感染进行至4～12周时,INH+DZ4预处理组Mtb感染小鼠的肺组织荷菌量较其它各组均显著偏低(P<0.05),肺组织的病理改变较其他各组也明显轻微。经滴鼻途径给予DZ4-FITC溶液4h后,小鼠肺组织冰冻切片在荧光显微镜下可见强烈的黄绿色荧光,并至少持续48h。对小鼠结核病模型的治疗结果显示,DZ4单独治疗组小鼠肺组织荷菌量及病理表现与未治疗组无显著差异;加用INH治疗的各组小鼠肺组织荷菌量与生理盐水组比较有显著下降(P<0.05),肺组织病理表现也明显轻微,但10-23DRz和INH联合治疗组与INH单独治疗组在肺组织荷菌量和病理表现上均无显著性差异。结论10-23DRz与INH联合预处理可有效降低Mtb感染小鼠的能力;本研究未发现10-23DRz对结核病具有治疗作用或辅助治疗作用。
Objective To investigate the effect of iclmRNA-specific 10-23 deoxyribozyme (DRz) on the infection of Mycobacterium tuberculosis (Mtb) in mice and its application alone or in combination with isoniazidum (INH) Therapeutic effect of tuberculosis in mice. METHODS: Mtb was pretreated with DZ4, INH, INH + DZ4-S or INH + DZ4, respectively. BALB / c mice were infected with Mtb pretreated with the above pre-treated Mtb. After a certain period of time, Mtb culture and pathology Change the observation. BALB / c mice were intranasally treated with DZ4-FITC solution to test the effect of intranasal administration. The mice model of tuberculosis was established by tail vein injection. The model mice were randomly divided into 5 groups (n = 10), treated with saline, DZ4, INH, INH, DZ4 and INH + DZ4- Week after the mouse lung tissue Mtb bacterial load detection and pathological changes were observed. Results Two weeks after Mtb infection, there was no significant difference in the amount of bacterial load in the lungs of mice (P> 0.05). In 4 to 12 weeks of infection, the infection of Mtb in infected mice with INH + DZ4 pretreatment group was significantly lower than that in other groups (P <0.05), and the pathological changes in lung tissue were also more obvious than those in other groups slight. After 4 hours of intranasal administration of DZ4-FITC solution, the frozen sections of mouse lung tissue showed strong yellow-green fluorescence under fluorescence microscope for at least 48 hours. The results of the treatment of mouse model of tuberculosis showed that there was no significant difference in the amount of bacterial load and the pathological appearance between the mice treated with DZ4 and the untreated group, (P <0.05). The pathological manifestations of lung tissue were also significantly lower. However, there was no significant difference in the amount of bacterial load and pathological manifestations between the 10-23DRz and INH combined treatment groups and INH alone treatment group. Conclusion 10-23DRz combined with INH pretreatment can effectively reduce the ability of Mtb infection in mice; this study did not find 10-23DRz tuberculosis has a therapeutic effect or adjuvant therapy.