治疗性新型结核疫苗保护力评价用动物模型的建立  

Establishment of a guinea pig model for evaluating the protective effects of new therapeutic vaccines against TB

作　　者：陈保文[1] 沈小兵[1] 卢锦标[1] 都伟欣[1] 苏城[1] 王国治[1] 

机构地区：[1]中国食品药品检定研究院结核病疫苗室,北京100050

出　　处：《中华微生物学和免疫学杂志》2013年第12期906-910,共5页Chinese Journal of Microbiology and Immunology

摘　　要：目的：建立治疗性新型结核疫苗抗结核保护力临床前评价用动物模型。方法采用单细胞耐多药结核分枝杆菌菌液感染豚鼠，感染途径为豚鼠腹股沟皮下，感染剂量每只为1000 CFU/0．2 ml。共进行2个实验，实验Ⅰ为在感染豚鼠3 d后，给予免疫治疗和/或化学治疗，分别于感染豚鼠后5、7、9周，取各组豚鼠4只进行解剖，观察肝、脾、肺的综合病变指数、脾脏结核杆菌荷菌量以及肝、脾、肺的组织病理改变；实验Ⅱ为在感染豚鼠14 d后，给予不同剂量免疫治疗和/或化学治疗，于感染豚鼠5周后，对各组豚鼠进行解剖，观察肝、脾、肺的综合病变指数和脾脏结核分枝杆菌荷菌量。结果在感染-治疗间隔时间为3d的实验Ⅰ中，感染豚鼠后第5周、7周和9周的结果显示，免疫治疗联合化疗、单一免疫治疗和单一化疗，都可有效抑制结核病变和降低脾脏结核杆菌荷菌量，与阴性对照比较均有统计学意义；同时，免疫治疗联合化疗的治疗方法优于单一的免疫治疗和单一的化疗，且随着停药时间延长，单一免疫治疗组和单一化疗组豚鼠脏器结核病变程度有大幅回升，而免疫治疗联合化疗组仅略有回升。在延长感染-治疗间隔时间为14 d的实验Ⅱ中，无论哪种治疗方法均能减轻结核病变和降低脾脏结核杆菌荷菌量，且免疫治疗联合化疗的治疗效果更佳。结论建立的治疗性新型结核疫苗抗结核保护力评价用豚鼠模型具有很好的重复性，可作为治疗性新型结核疫苗临床前研究效力评价动物模型。Objective To establish a suitable guinea pig model for evaluating the protective effects of new therapeutic TB vaccines in preclinical study .Methods The guinea pigs were subcutaneously injected with single-cell suspension of multi-drug resistant M.tuberculosis at a dose of 1000 CFU, 0.2 ml per animal.The study was divided into experimentⅠand experimentⅡ.In experimentⅠ, the guinea pigs were given immuno-therapy and/or chemical treatment on day 3 after infection .Four guinea pigs in each group were dissected at weeks 5, 7 and 9 after infection for evaluating lesion scores and histopathology changes of liver , spleen and lung, as well as bacterial load in spleen .In experimentⅡ, the guinea pigs were given immunotherapy and/or chemical treatment with different doses on day 14 after infection .All guinea pigs were dissected at week 5 after infection for evaluating lesion scores of liver , spleen and lung , as well as bacterial load in spleen .Results In experimentⅠ, all of the three treatments including immunotherapy combined with chemotherapy , immunotherapy alone and chemotherapy alone could effectively prevent organ lesion and reduce bacterial load in spleen , which were significantly different from negative control group .The immunotherapy combined with chemotherapy showed better treatment effects than other two treatments .Along with a prolonged period after drug withdrawal , the de-gree of organ lesion in immunotherapy group and chemotherapy group rebounded sharply , but only slightly in im-munotherapy combined with chemotherapy group .In experimentⅡ, animals in all treatment groups showed alle -viated organ lesion and reduced bacterial load in spleen .A relatively better treatment effect was observed in im-munotherapy combined with chemotherapy group .Conclusion The established guinea pig model of M.tubercu-losis infection showed an advantage of good repeatability .It might be used to evaluate the protective effects of new therapeutic vaccines against tuberculosis in preclinical study .

关 键 词：治疗性结核疫苗 保护力 豚鼠模型 

分 类 号：R-332[医药卫生]