摘要
目的观察噬菌体D29对结核病模型豚鼠体液免疫功能与细胞免疫功能的影响。方法采用皮下攻击法建立敏感和耐药结核分枝杆菌感染的结核病豚鼠模型，分别将感染敏感菌和耐药菌的豚鼠随机分为对照组、噬菌体组、利福平（RFP）组和联合化疗组。对照组给予0．9％氯化钠溶液隔日灌胃；RFP组给予RFP溶液隔日灌胃，每次给药剂量为15mg·kg^-1，每周3次；联合化疗组采用RFP＋乙胺丁醇＋吡嗪酰胺＋左氧氟沙星隔日灌胃，4种药物的剂量分别为15，25，25，6mg·kg^-1，每周3次；噬菌体组采用滴鼻的方式隔日给予噬菌体，每次1×10^8PFU（0．5mL），每周3次。均共治疗4～7周。观察治疗期间豚鼠血清中噬菌体中和抗体的动态变化，以及实验开始4周后豚鼠血清中白细胞介素．2（IL-2）、IL-4、γ干扰素（IFN-γ）的变化，并在电镜下观察巨噬细胞对噬菌体的吞噬情况。结果结核病模型豚鼠采用噬菌体治疗18d后，血清中均开始出现噬菌体中和抗体，抗体滴度与时间呈正相关。电镜观察发现巨噬细胞可以吞噬、消化部分噬菌体。敏感结核分枝杆菌感染模型采用利福平或噬菌体治疗4周后，血清中IL-2含量高于对照组；耐药结核分枝杆菌感染模型中RFP组、噬菌体组和联合化疗组的IL-2含量均高于对照组，其中噬菌体组血清IL-2含量最高，与对照组比较，差异有显著性（P〈0．05）。各组IL-4、IFN-γ均差异无显著性。结论噬菌体具有抗原的特性，可刺激机体产生中和抗体，同时可改善机体的细胞免疫功能，协同噬菌体杀灭机体内的结核分枝杆菌。
Objective To observe the effect of bacteriophage D29 on the humoral as well as cellular immune function of guinea pigs with a model of tuberculosis. Methods Guinea pig models of drug-sensitive and drug-resistant tuberculosis were set up by using the method of subcutaneous challenge with the corresponding bacteria. The animals infected with drug-sensitive or drug-resistant bacteria were then randomly divided into the following groups respectively： the control group, bacterophage group, rifampin（RFP） group and combined chemotherapy group. Guinea pigs of the control group were given each 0.9% sodium chloride solution administered by gastrogavage q. o. d.. Those of the RFP group were given each RFP solution containing 15 mg·kg^-1 of the drug administered by gastrogavage 3 times a week. Animals of the combined chemotherapy group were given each RFP ＋ ethambutol ＋ pyrazinamide ＋ levofloxacin administered by gastrogavage q. o. d. , the doses of the 4 drugs being 15,25,25 and 6 mg·kg^-1, respectively. Guinea pigs of the bacteriophage group were given each 1×10s PFU（0.5 mL） of bacteriophage D29 administered by nasal dripping 3 times a week. The course of treatment in all 4 groups lasted 4 - 7 weeks. The dynamic changes in the serum titer of neutralizing antibodies against the bacteriophage in animals of the bacteriophage group, the changes in serum levels of IL-1, IL-4, IFN-T in animals of all 4 groups 4 weeks after the beginning of the experiment were kept under observation. Phagocytosis of the bacteriophage by the macrophage was examined with electron microscopy. Results Neutralizing antibodies against the bacteriophage began to appear in the sera of the guinea pigs after they had been treated with the bacteriophage for 18 days and the titers of the antibodies were positively correlated with the time. Macrophages were shown to phagocytize and digest a portion of the bacteriophages as revealed by electron microscopy. The serum IL-2 contents in guinea pigs with the model of drug-sensitive tubercle bacilli infection were greater than those of the control animals after the former had been treated with RFP or the bacteriophage for 4 weeks. The serum IL-2 contents in guinea pigs with the drug-resistant tubercle bacilli infection were greater in those animals treated with RFP, bacteriophage and combined chemotherapy as compared with those in control animals. Among these, animals treated with the bacteriophage had the highest serum IL-2 content as compared with that of the controls （P〈0.05 ）. Differences between the different groups of animals with respect to serum IL-4 and IFN-γ levels were insignificant. Conclusion The bacteriophage was shown to be provided with antigenic characteristics. It could stimulate the organism to produce neutralizing antibodies and promote the cellular immune function of the body so that the latter could act svnergetically with the bacteriophage in the elimination of tubercle bacilli in the organism.
出处
《医药导报》
CAS
2006年第8期767-770,共4页
Herald of Medicine
关键词
噬菌体
结核分枝杆菌
豚鼠
免疫功能
Baterio phage
Tubercle bacilli
Guinea pig
Immune function
