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目的 评价异烟肼联合重组结核疫苗AEC/BC02 (BCG-CpG复合佐剂,即BCG-CpG-DNA+ Al)对结核分枝杆菌感染豚鼠的治疗效果.方法 选取30只无特定病原体(specific pathogen free,SPF)级豚鼠,在皮下注射结核分枝杆菌菌液[1000菌落形成单位(CFU)/只]1周后,按不同治疗方式分成4个组:即AEC/BC02组(6只),采用AEC/BC02疫苗进行肌肉免疫;INH组(6只),采用异烟肼10 mg进行灌胃治疗;INH+ AEC/BC02组,先采用异烟肼进行灌胃治疗2周后,再采用AEC/BC02疫苗进行肌肉免疫;生理盐水(NS)组(12只),作为阴性对照,仅注射NS.所有豚鼠在进行攻毒(注射结核分枝杆菌菌液)后第10周被解剖,以豚鼠肝、脾、肺脏病变指数评分评价脏器病变,并计算各脏器活菌载量(lg CFU).结果 AEC/BC02组、INH组和INH+ AEC/BC02组的整体脏器综合病变评分分别为(36.7±28.2)、(20.0±12.7)和(3.3±5.2)分,均低于NS组的(69.2±24.5)分,差异均有统计学意义(分别为q=4.37,P=0.023;q=6.61,P＜0.001;q=8.85,P＜0.001);INH+ AEC/BC02组整体脏器综合病变评分低于AEC/BC02组,差异也有统计学意义(q=3.88,P=0.049).INH+AEC/BC02组的脾脏活菌载量为(1.06±1.64) lg CFU,低于INH组的(3.55±1.90) lg CFU、AEC/BC02组的(4.21±0.78) lg CF及NS组的(4.73±0.79)lg CFU,差异均有统计学意义(分别为q=4.84,P=0.011;q=6.12,P=0.001;q=8.23,P＜0.001).INH+AEC/BC02组的肺脏活菌载量为(0.69±1.07) lg CFU,低于INH组的(2.66±1.70) lg CFU、AEC/BC02组的(3.01±0.90) lg CFU及NS组的(4.36±0.79) lg CFU,差异均有统计学意义(分别为q=4.43,P=0.021;q=5.21,P=0.006;q=9.50,P＜0.001);INH组的肺脏活菌载量低于NS组,差异也有统计学意义(q=4.39,P=0.022).结论 异烟肼和AEC/BC02疫苗联合使用优于单一治疗方式,能够明显减轻动物脏器病变,降低脾脏和肺脏的活菌载量.“,”Objective To evaluate the therapeutic effect of isoniazid combined with recombinant tuberculosis vaccine AEC/BC02 in Mycobacterium tuberculosis (MTB) infected guinea pigs.Methods Thirty guinea pigs chal lenged subcutaneously with 1000 CFU of MTB were divided into four groups one week later according to different treatment methods:normal saline (NS),AEC/BC02 vaccine,isoniazid (INH),and INH + AEC/BC02.In AEC/BC02 group,the animals were intramuscularly immunized with the single dose of AEC/BC02 vaccine six times at 10-day intervals.In INH group,each animal was treated with 10 mg isoniazid by oral gavage three times a week for 2 weeks.In INH±AEC/BC02 group,the guinea pigs firstly received INH treatment and then vaccinated with AEC/BC02 vaccine as the same dose and frequency as the INH group and AEC/BC02 group.NS group only received six doses of normal saline as a negative control.At ten weeks after infection,all guinea pigs were killed for necropsy.The liver,spleen and lung lesion indexes of guinea pig were scored to evaluate the organ lesions,and then tissue suspensions were cultured and calculated the bacterial loads (lg CFU).Results The gross pathological scores in AEC/BC02 group,INH group and INH+AEC/BC02 group were (36.7±28.2),(20.0±12.7) and (3.3±5.2) respectively,and significantly lower than that in NS group (69.2 ± 24.5) (q =4.37,P =0.023;q =6.61,P＜ 0.001;q=8.85,P＜0.001,respectively).There was also a significant difference between AEC/BC02 group and INH+ AEC/BC02 group (q=3.88,P=0.049).The spleen bacterial load in INH+AEC/BC02 group was (1.06±1.64) lg CFU and significantly lower than INH group ((3.55±1.90) lg CFU),AEC/BC02 group ((4.21±0.78) lg CFU) and NS group ((4.73±0.79) lg CFU) (q=4.84,P=0.011;q=6.12,P=0.001;q=8.23,P＜0.001,respectively).There was significant difference among INH group,AEC/BC02 group and NS group.The lung bacterial load in INH+AEC/BC02 group was (0.69± 1.07) lg CFU and significantly lower than INH group ((2.66± 1.70) lg CFU),AEC/BC02 group ((3.01±0.90) lg CFU) and NS group ((4.36±0.79) lg CFU)(q=4.43,P=0.021;q=5.21,P=0.006;q=9.50,P＜0.001,respectively).Also the significant difference was observed between INH group and NS group (q=4.39,P=0.022).Conclusion INH in combination with AEC/BC02 vaccine was superi or to single isoniazid or AEC/BC02 treatment,could reduced the organ lesions and lowered the bacterial loads in spleens and lungs.