氯法齐明抗结核分枝杆菌的体内外活性研究

目的 评价氯法齐明(clofazimine,CLF)在体外及体内抗结核分枝杆菌的活性,为临床应用提供依据.方法 应用微孔板指示剂法,测定氯法齐明对结核分枝杆菌标准株H37Rv及临床分离耐多药结核分枝杆菌(30株)的MIC;建立小鼠静脉感染H37Rv的结核病模型(105 CFU/只),根据氯法齐明的不同剂量,分为3个治疗组:20 mg/kg,每周给药5次(CLF-1组);10 mg/kg,每周给约5次(CLF-2组);20 mg/kg,每周给药2次(CLF-3组);治疗30 d后进行肺、脾组织活菌计数,应用单冈素方差分析,比较氯法齐明在小鼠体内的抗结核分枝杆菌活性.结果 氯法齐明对结核分枝杆菌H37Rv的MIC为0.12～0.24 μg/ml;对30株耐多药结核分枝杆菌临床分离株的MIC为0.12～1.92 μg/ml.在小鼠结核病治疗模型中,3个治疗组的小鼠肺活菌计数分别较空白对照组降低2.92、1.78和1.39 lg CFU,均具有统计学意义(F=74.09,P＜0.01).结论 氯法齐明具有较好的体外及体内抗结核分枝杆菌活性,值得进一步研究.

Activities of clofazimine against Mycobacterium tuberculosis in vitro and in vivo

objective To evaluate the in vitro and in vivo antituberculous activities of clofazimine.Methods The MIC of clofazimine against H37 Rv and 30 MDR-TB clinical strains were determined by microplate Alamar blue assays.Female BALB/c mice were infected with M.tuberculosis H37Rv(105 CFU/mouse).The infected mice were divided into the following groups:a control group,treated with saline 5 times per week;isoniazid treatment group,25 mg/kg,5 times per week;clofazimine 20 mg/kg group,5 times per week;clofazimine 10 mg/kg group,5 times per week,and another clofazimine 20 mg/kg group,but the drug was given twice weekly.The drugs and saline were administered by gavage,and the treatment lasted for 30 days after infection.Five mice from each group were assessed for bacterial CFU count and organ weights of the lung and spleen on day 30.Results The MIC of clofazimine against M.tuberculosis H37Rv Was 0.12-O.24 μg/ml,and the MIC against 30 MDR-TB clinical strains ranged from 0.12 to 1.92 μg/ml.In the muriue model,clofazimine treatments decreased the CFU by 1.39-2.92 lg as compared to that of the control group on day 30.Conclusions Clofazimine has in vitro and in vivo activities against M.tuberculosis.