摘要
目的:观察噬菌体D29对患耐药结核病豚鼠的治疗作用.方法:采用皮下攻击法建立耐药结核病豚鼠模型,建模成功后随机将动物分为对照组、利福平(RFP)组、联合化疗组、噬菌体组4组.分别给予生理盐水、RFP单独、多种抗结核药物联合灌胃、噬菌体D29滴鼻,3次/wk,隔日给药.于治疗4,7wk后观察各组动物的一般情况、脏器质量指数(WI)、脏器病理组织学改变.脾脏结核分枝杆菌定量培养,并用ELISA方法检测血液中IL-2,IL-4,IFN-γ含量.结果:RFP组、联合化疗组在给药4wk内,体质量增长量明显小于对照组(P<0.05),而噬菌体组的体质量增长正常,与对照组相比较差异不显著.治疗4wk时各治疗组的病变指数均低于对照组,其中噬菌体组病变程度最轻,荷菌量(CFU)最低,差异具有统计学意义(P<0.05).7wk时动物的均一性对照组、RFP组较差,噬菌体组、联合化疗组较好.病理组织学改变噬菌体组、联合化疗组肺脏以纤维化、增生结节为主,脾脏很少有干酪样坏死;对照组肺脏可见大量Langhans细胞,以增生结节为主,脾脏较多干酪样坏死;IL-2含量RFP组、噬菌体组、联合化疗组均高于对照组,其中以噬菌体组含量最高,差异具有统计学意义(P<0.05).各组IL-4,IFN-γ均无显著性差异.结论:噬菌体D29可减轻耐药结核病豚鼠的脏器病变程度和脏器CFU,可改善机体细胞免疫功能,协同噬菌体杀灭机体内的结核菌,对豚鼠无副作用,有望作为新型抗结核药物的开发对象.
AIM： To explore the effect of bacteriophage D29 on resistant tuberculosis in vivo and to evaluate the possibility of using it as an anti-tuberculosis agent. METHODS： Guinea pigs infected with resistant M. tuberculosis were randomly divided into 4 groups： control group, rifampin treated group, co-chemotherapy group and phage treated group. Experiments were conducted, in which either saline water or fifampin or four drugs （including rifampin, ethambutol, pyrazinamide and levofloxaein ） were administrated through gastro-esophagus, or phage through nasa by the interval of 3 times per 1 week. After 4-and 7-week therapy, pathological degree, lung or liver or spleen weight index and quantitative cultures were assessed. The lungs, livers, and spleens from guinea pigs were used to assess the histo-pathologic changes induced by different therapy at each sacrifice time. The concentration of IL-2, IL-4 and IFN-gamma was measured by enzyme-linked immune-sorbent assay. RESULTS： When guinea pigs with resistant tuberculosis were treated with phage D29 for 4 weeks, the pathological degree and the quantitative cultures of hi. tuberculosis in spleen were less than those in control group. Mainly fibrosis and little necrosis were observed in the lungs of phage treated group and co-chemotherapy group, but most hyperplasia and langhans cells in the lungs and caseous necrosis in the spleen were seen in control group. The cytokine IL-2 secretion capability of phage treated group was statistically different compared with that in control group. Other groups had higher cytokine, but with no statistically significant difference. CONCLUSION： In vivo, phage D29 results in a reduction in organ pathological degree and quantitative cultures of mycobaeteria. The application of phage D29 may be a novel and hopeful strategy to combat tuberculosis.
出处
《第四军医大学学报》
北大核心
2009年第17期1576-1579,共4页
Journal of the Fourth Military Medical University
关键词
分枝杆菌噬菌体
结核
抗药性
微生物
药效学
免疫
bacteriophage（phage）
tuberculosis
drug resistant, microbial
pharmic-therapeutic efficacy, imumunity
