分枝杆菌噬菌体对感染敏感株结核菌豚鼠的治疗作用.doc

噬菌体D29对感染结核分枝杆菌敏感株豚鼠的治疗作用 彭丽 罗永艾 陈保文 黎友伦 沈小兵 苏城 王国治 [摘要]目的 观察噬菌体D29对感染结核分枝杆菌敏感株的豚鼠的治疗作用，探讨其能否成为一种治疗结核病的新药。方法 采用皮下攻击法建立敏感结核病豚鼠模型，感染成功后动物被随机分为对照组、利福平(rifampin，RFP)组、噬菌体组。分别给予不治疗、RFP 25mg/kg灌胃、噬菌体D29 108 噬菌斑形成单位（plaque-forming unit，PFU）/0.5ml 滴鼻，每周3次，隔日给药。治疗4周后，每组取4～5只豚鼠进行解剖，观察动物一般情况、脏器肉眼病变程度、脏器重量指数、脏器病理组织学检查以及肺脏和脾脏结核分枝杆菌的定量培养。结果 采用噬菌体、RFP治疗4周后豚鼠结核病模型的脏器病变指数显著低于对照组 (p0.05)，噬菌体组的肺脏荷菌量显著低于对照组 (p0.05)，RFP组的肺脏荷菌量低于对照组 (p0.05)。病理组织学上，噬菌体组豚鼠的肺脏以纤维化为主；脾脏很少有干酪样坏死，以增生性结节为主。对照组肺脏见大量Langhans 细胞，以增生结节为主；脾脏较多干酪样坏死。结论 噬菌体D29可减轻结核病豚鼠的脏器病变程度和脏器荷菌量，具有与RFP接近，甚至更好的疗效，对豚鼠没有副作用，有希望作为新型抗结核药物的开发对象。 [关键词] 分枝杆菌噬菌体；分枝杆菌，结核；药效学 Utility of bacteriophage D29 in treatment of guinea pigs infected with sensitive Mycobacterium tuberculosis Peng Li*, Luo Yong-ai, Chen Bao-wen, Li You-lun, Shen Xiao-bing, Su Cheng, Wang Guo-zhi. * Department of Pulmonary Disease, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016 [Abstract] Objective To explore the effect of bacteriophage D29 to M.tuberculosis in vivo and evaluate the possibility of it as anti-tuberculosis agent. Methods Guinea pigs , which were infected with sensitive M. tuberculosis, were randomly divided 作者单位：400016，重庆医科大学附属第一医院（彭丽，罗永艾, 黎友伦）；100050，中国药品生物制品检定所（沈小兵，陈保文，苏城，王国治） into 3 groups: control (i.e. non-therapy) group, rifampin treated group and phage treated group. Experiments were done in which either rifampin 25 mg per kilogram of weight through gastroesophagus adiministration, or phage D29 108 PFU through aerosols injection by the interval of 3 times per 1 week. 4 to 5 pigs per group were sacrificed at week 4 post therapy, including pathological degree, lung or liver or spleen weight index, and quantitative cultures to assess the growth of M.tuberculosis in lung or spleen. In addition, the lungs, livers, and spleens from one guinea pig were used to assess the histo-pathologic changes induced by different therapy method at each sacrifice time. Results When guinea pigs with tuberculosis had been treated with