耐药结核分枝杆菌潜伏-复发感染动物模型的研究进展

The research prospect of animal models of drug-resistant Mycobacterium tuberculosis latent-relapse infection

潜伏结核感染(latent tuberculosis infection,LTBI)复发是新发结核病的主要来源,其中耐药结核病所占比例较大,使耐药LTBI复发的防控成为结核病研究的重点。耐药结核分枝杆菌潜伏-复发感染动物模型是开展耐药结核病防控相关机制研究、抗耐药结核分枝杆菌药物和疫苗研究的基础。目前耐药结核分枝杆菌感染动物模型缺乏,而已有的结核分枝杆菌标准株H37Rv潜伏-复发感染模型存在缺陷,如小鼠模型的潜伏期荷菌量偏高、复发期变异大,而猴模型的潜伏期和复发期不可预测。模型的可控性差使其应用困难,且缺乏可用的免疫学评价指标,导致远期复发无法预测。因此,基于现有H37Rv潜伏-复发感染动物模型的制备方法,展望耐药结核分枝杆菌潜伏-复发感染动物模型可能存在的缺陷,通过选用新的抑菌剂和诱导剂,制备有稳定潜伏期、潜伏时长适中、复发起点和复发水平变异小的动物模型,是未来耐药结核分枝杆菌潜伏-复发感染动物模型研究的方向。

The new cases of tuberculosis mainly come from the relapse of latent tuberculosis infection（LTBI）,and the growing proportion of drug-resistant Mycobacterium tuberculosis（DR-Mtb）among LTBI makes DR-LTBI the key point of tuberculosis prevention and control.The animal model of DR-Mtb latentrelapse infection is the foundation for basic research,anti-DR-Mtb drug development and vaccine evaluation.However,the lack of a DR-Mtb animal model today presents a hurdle.The animal model of latent-relapse infection based on drug-sensitive strain H37 Rv still has concerns such as high bacterial loads in the latent phase and large variation in the relapse phase in mice,and unpredicted latent and relapse phases in monkeys.These concerns limit its application.Furthermore,the lack of immune parameters in the evaluation makes the forward relapse unpredicted. The strategies and research progresses on the improvement of the current models are reviewed in this paper.