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目的 研究、比较4种结核分枝杆菌增殖期抗原基因抗小鼠结核感染的作用,为开发新型结核病免疫治疗制剂提供实验依据.方法 将70只BALB/c小鼠采用数字表法随机分为7组,每组10只.以6.4×105菌落形成单位(CFU)结核分枝杆菌标准株H37Rv尾静脉注射感染小鼠后第3天,分别用生理盐水、pVAX1载体、微卡菌苗、ag85a DNA、rv1291c DNA、rv1419 DNA和rv2223c DNA进行肌内注射,每2周1次,共3次,免疫结束后2周杀鼠,分别取肺和脾观察其病理改变、称取肺和脾的质量、做菌落计数.结果 肺组织病理显示:生理盐水组肺组织病变严重、广泛;载体组病变也较严重、广泛,但比生理盐水组略轻;微卡菌苗组、ag85a DNA组、rv1291c DNA组、rv1419 DNA组和rv2223c DNA组肺组织病变有不同程度减轻,病变局限,部分区域肺泡结构完整、清晰,细胞分布均匀.与生理盐水组相比,ag85a DNA组、rv1291c DNA组、rv1419 DNA组肺菌落计数分别减少0.53 lg CFU、0.67 lg CFU、0.41 lg CFU(x2 =27.07,P＜0.01);脾菌落计数分别减少0.43 lg CFU(t＞3.004,P＜0.05)、0.34 lg CFU(t＜3.004,P＞0.05)、0.41 lg CFU(t＞3.004,P＜0.05);微卡菌苗组和rv2223c DNA组肺、脾菌落计数与生理盐水组比较均有所减少,但差异无统计学意义(t值均＜3.004,P值均＞0.05).结论 结核分枝杆菌增殖期抗原基因rv1291c和rv1419 DNA与ag85a DNA具有相似的抗结核治疗效果,而rv2223c DNA无明显治疗作用.“,”Objective To compare the anti-tuberculosis effects of four kinds of genes encoding the antigens in proliferation phase of M.tuberculosis in mouse tuberculosis (TB) model,and provide experimental basis for developing new TB immunotherapy agents.Methods Seventy female BALB/c mice were infected via the tail vein with 6.4× 105 CFUs of M.tuberculosis H37Rv,then randomly divided into 7 groups and treated as follow at the third day after infection:saline,plasmid vector pVAX1,M.vaccae vaccine,ag85a DNA,rv1291c DNA,rv1419 DNA and rv2223c DNA,which were injected intramuscularly 3 times at two-week intervals.The mice were sacrificed at two weeks after the final immunization.The lungs and spleens from the mice were taken and their pathological changes,weights and number of mycobacterial colony were examined.Data were expressed as means and standard deviations.Results The lung histopathological examination showed that the lesions were severe and extensive in saline group,lighter in plasmid vector pVAX1 group than those in saline group,slight and limited in the M.vaccae vaccine,ag85a DNA,rv1291c DNA,rv1419 DNA and rv2223c DNA groups with relatively clear and normal structure of alveoli.Compared with saline group,ag85a DNA group,rv1291c DNA group and rv1419 DNA group reduced the pulmonary bacterial loads respectively by 0.53 lg CFU,0.67 lg CFU and 0.41 lg CFU (x2 =27.07,P＜0.01);spleen bacterial loads respectively by 0.43 lg CFU (t＞3.004,P＜0.05),0.34 lg CFU (t＜3.004,P＞0.05),and 0.41 lg CFU (t＞3.004,P＜0.05);M.vaccae vaccine and rv2223c DNA groups also decreased lung and spleen bacterial loads,but there were not significant differences (t＜3.004,all P＜0.05).Conclusion M.tuberculosis rv1291c and rv1419 genes encoding the antigens in proliferation period had better irnmunotherapeutic effects on TB,which were similar to ag85a DNA in mice.Rv2223c DNA had not obvious immunotherapeutic effect.