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Study on guinea pig model of acute infection with Mycobacterium tuberculosis H37Rv strain |
KANG Jian1 XU Chengming1 ZHANG Wei2 BAI Yinlan1 HAN Wendong3 SUN Zhiping3 XU Zhikai1 WANG Limei1▲ |
1.Department of Microbiology and Pathogenic Biology, Air Force Military Medical University, Shaanxi Province, Xi′an 710032, China;
2.Department of Pediatric, Tangdu Hospital, Air Force Military Medical University, Shaanxi Province, Xi′an 710032, China;
3.the Third Level Biosafety Laborator, Fudan University, Shanghai 200032, China |
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Abstract Objective To establish a guinea pig model of acute infection with Mycobacterium tuberculosis (Mtb) H37Rv strain. Methods Eighteen guinea pigs were divided into six groups: blank-dose group, subcutaneous high-dose group, subcutaneous low-dose group, intranasal high-dose group, intranasal middle-dose group and intranasal low-dose group according to random number table method. There were three guinea pigs in each group. Subcutaneous high-dose group and subcutaneous low-dose group was infected with Mtb H37Rv PBS suspension of 2×106 CFU/200 μL and 1×106 CFU/200 μL respectively. Intranasal high-dose group, intranasal middle-dose group and intranasal low-dose group was infected with Mtb H37Rv PBS suspension of 5×105, 5×104 CFU/50 μL and 5×103 CFU/50 μL respectively. After four weeks of infection, the number of bacteria and histopathological changes of lung and spleen in each group were detected. Results After four weeks of infection, the number of Mtb in lung and spleen of subcutaneous high-dose group was higher than that of subcutaneous low-dose group (P < 0.05). After four weeks of infection, the number of Mtb in lung of subcutaneous high-dose group was higher than that of intranasal high-dose group (P < 0.05). After four weeks of infection, the lung tissues of guinea pigs in subcutaneous high-dose group, subcutaneous low-dose group and intranasal high-dose group were obviously congested and the alveolar wall were thickened; the lung tissue of guinea pigs in intranasal middle-dose group and intranasal low-dose group had only slight hyperemia. After four weeks of infection, the pathological changes of spleen tissue in each group were not obvious. Conclusion The guinea pig model of acute infection with Mtb H37Rv is established successfully, which provides the research foundation for novel tuberculosis vaccines and new drugs.
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[1] Global tuberculosis report 2017 [D/OL]. http://www.who.int/tb/en/.
[2] Gupta UD,Katoch VM. Animal models of tuberculosis [J]. Tuberculosis(Edinb),2005,85(5-6):277-293.
[3] Zhan L,Tang J,Sun M,et al. Animal models for tuberculosis in translational and precision medicine [J]. Front Microbiol,2017,8:717.
[4] 师长宏,徐志凯,范雄林.结核分枝杆菌感染的动物模型[J].国外医学:微生物学分册,2004,27(4):31-34.
[5] Kashino SS,Napolitano DR,Skobe Z,et al. Guinea pig model of Mycobacterium tuberculosis latent/dormant infection [J]. Microbes Infect,2008,10(14-15):1469-1476.
[6] Myllym?覿ki H,Niskanen M,Oksanen KE,et al. Animal models in tuberculosis research—where is the beef? [J]. Expert Opin Drug Discov,2015,10(8):871-883.
[7] 黎友伦,王国治,罗永艾.结核分枝杆菌潜伏感染动物模型及评价[J].中华结核和呼吸杂志,2005,28(8):552-554.
[8] 肖和平.耐药结核病化学治疗指南(2009)[J].中华结核和呼吸杂志,2010,33(7):485-497.
[9] 董江涛,张万江.结核分枝杆菌感染小鼠动物模型的建立及研究进展[J].中国病原生物学杂志,2011,6(8):621-623.
[10] 卢锦标,邓海清,陈保文,等.结核分枝杆菌潜伏感染豚鼠模型的建立和验证[J].中华微生物学和免疫学杂志,2013,33(12):900-905.
[11] Zhang Y,Yew WW,Barer MR. Targeting persisters for tuberculosis control [J]. Antimicrob Agents Chemother,2012,56(5):2223-2230.
[12] Wang P,Wang L,Zhang W,et al. Immunotherapeutic efficacy of recombinant Mycobacterium smegmatis expressing Ag85B-ESAT6 fusion protein against persistent tuberculosis infection in mice [J]. Hum Vaccin Immunother,2013,10(1):1-9.
[13] Steven C,Derrick,Idalia M,et al. Immunogenicity and protective efficacy of novel Mycobacterium tuberculosis antigens [J]. Vaccine,2013,31(41):4641-4646.
[14] 张昊凌,张志勇.结核分枝杆菌感染动物模型的研究进展[J].微生物与感染,2012,7(3):184-189.
[15] 王应辉,王洪海,曹健,等.潜伏性结核分枝杆菌感染动物模型[J].中国感染控制杂志,2011,10(4):312-315.
[16] 王豫萍,王和.结核分枝杆菌稳定L型致病性的研究[J].上海医学检验杂志,2001,16(z1):14-16.
[17] 路延之,王丽梅,康健,等.结核分枝杆菌亚单位疫苗Ag85b-ESAT-6+Hsp65-IL-2的安全性评价研究[J].中国人兽共患病学报,2016,32(11):945-951.
[18] 王平,王丽梅,张薇,等.结核分枝杆菌Ag85B-ESAT-6融合蛋白重组耻垢分枝杆菌对小鼠的免疫原性研究[J].中国防痨杂志,2012,34(3):145-149.
[19] 宁唤唤,路延之,康健,等.分枝杆菌持续感染小鼠模型的建立及其特征分析[J].中国病原生物学杂志,2017, 12(3):219-223.
[20] 黎友伦,陈保文,徐苗,等.结核分枝杆菌潜伏感染豚鼠模型的建立[J].中华结核和呼吸杂志,2010,33(9):684-687.
[21] 卢锦标,杨蕾,苏城,等.重组AEC/BC02疫苗联合化疗在豚鼠模型中的抗结核效果[J].中华微生物学和免疫学杂志,2018,38(6):414-419.
[22] 张晓东,王洪生.结核分枝杆菌感染动物模型的研究进展[J].国际皮肤性病学杂志,2012,38(3):190-193.
[23] 李定越,卢润生,蒋绍双.结核病实验动物模型[J].四川医学,2003,24(7):761-762.
[24] Hernfndez-Pando R,Pavon L,Orozcoe H,et al. Correlation between the kinetics of Thl,Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis [J]. Immunology,1996,89(1):26-33.
[25] Dorhoi A,Reece ST,Kaufmann SH. For better or forworse:the immune response against Myeobacterium tuberculosis balances pathology and protection [J]. Immunol Rev,2011,240(1):235-251. |
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