肺痨康治疗与KatG基因突变相关的耐异烟肼肺结核分子机制初探  

Molecular Mechanism of Isoniazid Resistant Tuberculosis Associated with Kat G Gene Mutation by Treatment with Feilaokang

作　　者：王燕平[1] 叶品良[1] 张传涛[2] 卢润生[3] 卢振方[1] 陈欢[1] 

机构地区：[1]成都中医药大学,成都610075 [2]成都中医药大学附属医院感染科,成都610072 [3]四川省疾病预防控制中心,成都610041

出　　处：《浙江中西医结合杂志》2016年第5期410-413,共4页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金资助项目(No.81173382)

摘　　要：目的探讨肺痨康治疗耐异烟肼肺结核的分子机制是否与Kat G基因突变发生回复相关。方法 SPF级昆明种小鼠80只随机分为标准菌株组、对照组、异烟肼组、肺痨康组,各20只;分别给予生理盐水、生理盐水、异烟肼液、肺痨康液连续灌胃56天。处死小鼠解剖分离出肺组织,每组随机抽取1~2只感染小鼠肺组织提取结核分枝杆菌DNA进行全基因组检测。分析各组小鼠肺组织耐药分枝结核杆菌基因突变情况。结果 （1）标准菌株组基因序列与参考值一致;对照组与参考值比较仅Kat G基因突变。（2）与对照组比较,异烟肼组、肺痨康组Kat G基因突变位点未见基因回复现象,但发现更多突变位点。（3）与异烟肼组比较,肺痨康组不仅存在相当大部分新生突变位点重合现象,还出现仅肺痨康组存在的新生突变位点,其密码子对氨基酸表达影响程度达＂HIGH＂。结论异烟肼、肺痨康对Kat G基因突变导致的耐异烟肼肺结核均有治疗作用。肺痨康组治疗作用可能与新突变位点（RV0063）改变有关。Objective To explore the molecular mechanism of Feilaokang treating isoniazid-resistant tuberculosis is related to Kat G gene mutations with or without reply. Methods Eighty SPF mice were randomly divided into standard strain group, control group, isoniazid group, and Feilaokang group, in each group of 20 mice. Mice in the above groups were given saline, saline, isoniazid, and Feilaokang by gavage for 56 d, respectively, then the mice were sacrificed and the lung tissues were dissected and isolated, and 1-2 of the DNA infected mice in each group were randomly selected to extract mycobacterium tuberculosis. Results The gene sequence of mycobacterium tuberculosis in standard strain group was consistent with reference; that of control group had Kat G gene mutation. Compared with control group, isoniazid and Feilaokang groups had more Kat G gene mutations with out reply. Compared with isoniazid group, Feilaokang group had more de novo Kat G gene mutations, and some of the mutations were only observed in Feilaokang group. The codon of the mutation had high accuracy in specifying the amino acid.Conclusion Both of Isoniazid and Feilaokang can treat isoniazid-resistant tuberculosis induced by Kat G gene mutations. The effect of Feilaokang may be related to the new mutation site RV0063.

关 键 词：耐药肺结核 肺痨康 Kat G基因突变 分子机制 

分 类 号：R521[医药卫生—内科学]