抗生素联合卡介苗治疗结核病的动物模型评价  

Therapeutic evaluation of Mycobacterium tuberculosis-infected guinea pig model treated in combination with antibiotics and BCG vaccine

作　　者：都伟欣[1] 苏城[1] 沈小兵[1] 杨蕾[1] 陈保文[1] 王国治[1] 卢锦标[1] DU Wei-xin;SU Cheng;SHEN Xiao-bin;YANG Lei;CHEN Bao-wen;WANG Guo-zhi;LU Jin-biao(Division of Tuberculosis Vaccines, National Institutes for Food and Drug Control,Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Beijing 102269, China)

机构地区：[1]中国食品药品检定研究院结核病疫苗室卫生部生物技术产品检定方法及其标准化重点实验室,北京102269

出　　处：《微生物学免疫学进展》2018年第2期9-14,共6页Progress In Microbiology and Immunology

基　　金："十二五"国家科技重大专项(2012ZX10004701)

摘　　要：目的用豚鼠模型初步评价抗生素联合卡介苗治疗结核病的可行性。方法用高剂量Mtb皮下攻击豚鼠2周后,将重组ESAT6-CFP10(EC)变态反应原皮试阳性的豚鼠随机分成4组:NS组、BCG组、抗生素组、抗生素+BCG组。抗生素+BCG组接受异烟肼(isoniazid,INH)和利福喷丁(rifapentine,RFT)的联合化疗,1次/周,共3次,给药结束后,每只豚鼠皮下免疫1/10人用剂量BCG;BCG组每只豚鼠仅皮下免疫1/10人用剂量BCG;抗生素组仅给药INH和RFT,1次/周,共3次;NS组给予生理盐水作为阴性对照。全部豚鼠于攻毒13周后安乐死解剖,评价肝、脾、肺的脏器综合病变指数,计算脾脏活菌载量(lg CFU),并对肝、脾、肺脏器做组织病理检查。结果 NS组、BCG组、抗生素组和抗生素+BCG组的脏器评分分别为83±8、81±10、45±28和33±14。其中,BCG组与NS组差异无统计学意义;抗生素组和抗生素+BCG组与NS组差异均有统计学意义(分别q=6.84,P<0.001;q=9.02,P<0.001),两组与BCG组比较,差异也均有统计学意义(q=6.44,P<0.001;q=8.63,P<0.001);但抗生素组与抗生素+BCG组差异无统计学意义。抗生素+BCG组豚鼠的脾脏活菌载量为(3.62±1.13)lg CFU,与NS组的(4.92±0.52)lg CFU和BCG组的(5.20±0.43)lg CFU比较,差异均有统计学意义(q=5.54,P<0.01;q=6.72,P<0.001)。抗生素组脾脏活菌载量为(4.39±0.50)lg CFU,与其他各组的差异均无统计学意义。病理组织切片显示各组病变程度由重到轻依次为BCG组>NS组>抗生素+BCG组≈抗生素组。结论化疗后免疫1针BCG的治疗效果较差,多针次的BCG免疫效果还需进一步研究。Objective To evaluate the potential therapeutic effect of antibiotics combined with BCG in Mycobacterium tuberculosis （ Mtb ） -infected guinea pig as an animal model. Methods Two weeks after guinea pigs were challenged subcutaneously with a high dose of Mycobacterium tuberculosis, the animals with the positive skin test result of the recombinant ESAT6-CFP10 allergen were then randomly divided into four groups： NS, BCG, antibiotics, and antibiotics ＋ BCG. In antibiotics ＋ BCG group, guinea pigs firstly received INH（isoniazid）and RFT（rifapentine） treatment once a week for a total three times, and then were vaccinated with 1/10 dose of BCG vaccine. In BCG group animals were only vaccinated with 1/10 dose of BCG vac- cine whereas in antibiotics group animals only received INH and RFF treatment as the same dose and frequency as the antibi- otics ＋ BCG group. Thirteen weeks after challenge, all guinea pigs were in euthanasia and for necropsy. Results The gross pathological scores in NS, BCG, antibiotics, and antibiotics ＋ BCG group were 83 ± 8, 81 ±10, 45 ±28 and 33±14, respec- tively. There was no a statistical meaning between BCG and NS group. The significant difference was observed between the an- tibiotics and NS group （ P 〈 0.001 ）, and also observed between antibiotics ＋ BCG and NS group （ P 〈 0.001 ）. Both the anti- biotics and antibiotics ＋ BCG group had a significantly lower gross pathological scores than the BCG group （ both P 〈 0.001 ） ,but there was no a statistical meaning between the antibiotics and antibiotics ＋ BCG group. The spleen bacterial load in the antibiotics ＋ BCG group was {3.62±1.13} lg CFU and signifi- cantly lower than those in NS group （4.92 ± 0.52） lg CFU and BCG group （5.20 ± 0.43） lg CFU （P 〈 0.01, P 〈 0.001, re-spectively}. The spleen bacterial load in the antibiotic group was （4.39 ± 0.50） lg CFU, and had no a statistical meaning compared to those in other groups. The histopathologieal examination of liver, splee

关 键 词：抗生素 卡介苗 豚鼠 联合 保护力 

分 类 号：R52[医药卫生—内科学] R392[医药卫生—临床医学]