IFN-γ和IL-10作为药物抗结核活性评价指标的可行性考察  

The Feasibility of IFN-γ and IL-10 as Surrogate Markers to Evaluating the Activity of Drugs Against Mycobacterium Tuberculosis

作　　者：赵伟杰[1] 郑梅琴[2] 王彬[1] 付雷[1] 李芃[2] 赵志刚[3] 

机构地区：[1]首都医科大学附属北京胸科医院,北京市结核病胸部肿瘤研究所药物研究室,北京101149 [2]首都医科大学附属北京胸科医院,北京市结核病胸部肿瘤研究所,药剂科,北京101149 [3]首都医科大学附属北京天坛医院药剂科学部,北京100050

出　　处：《中国药学杂志》2014年第9期759-763,共5页Chinese Pharmaceutical Journal

基　　金：十二五“重大新药创新”科技重大专项(2012ZX09303002)

摘　　要：目的探讨细胞因子是否可以作为一项指标评价药物对小鼠结核模型的疗效。方法 75只BALB/c小鼠雾化感染建立小鼠结核模型,分为13组,药物治疗2月以后,取血并做全肺活菌(CFU)计数;ELISA法检测血清中的γ-干扰素(IFN-γ)和白介素10(IL-10)的浓度;以全肺活菌计数作为药物对小鼠结核活性的标准,检验血中的γ-干扰素和白介素10的含量及二者的比值与小鼠肺中全肺活菌的相关性并进行线性回归。结果①全肺活菌计数:除左氧氟沙星(Lfx)和对氨基水杨酸(PAS)组以外,其余各治疗组与空白对照组相比均有统计学差异;各治疗组与阳性对照组(利福平+异烟肼+吡嗪酰胺,RHZ)相比均有统计学差异。②γ-干扰素:除左氧氟沙星、对氨基水杨酸组以外的各治疗组与空白对照组均有统计学差异;各治疗组与阳性对照组相比没有统计学差异。③白介素10:各治疗组与空白对照组、各治疗组之间均没有统计学差异。④γ-干扰素/白介素10:氯法齐明、利奈唑胺+丙硫异烟胺、利奈唑胺+氯法齐明、利奈唑胺+阿米卡星、利福平+异烟肼+吡嗪酰胺组与空白对照组相比有统计学差异,各治疗组之间均没有统计学差异。⑤γ-干扰素、白介素10、γ-干扰素/白介素10与全肺活菌呈正相关,确定因子r2分别为0.688、0.237、0.582。结论外周血中γ-干扰素的含量可以用来判断治疗方案是否有效,但不适宜作为生物标记物来预测体内结核菌的数量。OBJECTIVE To study the probability of IFN-＇y and IL-10 being surrogate markers for evaluating the anti-TB activity of drugs. METHODS 75 BALB/c mice infected with H37Rv using a Glas-col inhalation exposure system, were randomized into 13 groups. After 2 months of therapy, the numbers of CFU in the lungs and the levels of IFN-γ and IL-10 in blood were determined. The relevance of IFN-＇y, IL-10 concentrations, the ratio of IFN-γ/IL-10 and CFU were evaluated respectively. RESULTS ①CFU enu meration： the CFU of treatment groups except Lfx and PAS were significantly different from that of negative control group; the CFU of every treatment groups were significantly different from that of positive group. ②Levels of IFN-γ： the levels of IFN-γ in peripheral blood of treatment groups except Lfx and PAS were significantly different from that of negative control group; the IFN-γof every treat ment groups were significantly different from that of positive group. ③IL-lO：There were differences exiting neither between treatment groups and negative group nor between any two treatment groups. ④IFN-γ/IL-10： significantly differences were displayed between CLF, LZD ＋ Pto, LZD ＋ CLF, LZD ＋ Am, HRZ and negative group respectively, while no significantly differences showed between any pair of treatment groups.⑤positive corrections were displayed between IFN-γ IL-10, IFN-γ/IL-10 and CFU, certainty factor（ r^2 ） were 0. 688,0. 237,0. 582. CONCLUSION The levels of IFNγmay be used to evaluate the anti-TB activity of drugs and may not be the surrogate markers to predict the CFU in vivo.

关 键 词：结核 活菌计数 Γ-干扰素 白介素-10 

分 类 号：R965[医药卫生—药理学]