结核分枝杆菌耐利福平药物机理的初步研究

目的通过诱导试验观察结核菌产生耐利福平药物的全过程，初步分析结核菌耐该药的机理。方法采用诱导试验、聚合酶链反应—单链构象多态性(PCR-SSCP)和序列分析，对经不同药物浓度传代培养后的结核菌强毒株（H₃₇Rv）和36株临床耐药分离株进行分析。结果在诱导到第7代时，H₃₇Rv的PCR-SSCP电泳出现异常，经测序证实在513位点发生基因突变。36株临床耐药分离株中有23株发生突变，为63.9% (23/36)；其中有5株与诱导株基因突变位点相同。结论用药物不间断的刺激结核菌，是产生结核菌耐利福平药物的重要原因。

The preliminary study on rifampicin-resistant mechanism of Mycobacterium tuberculosis

Objective To study the mechanism of drug resistance in M. tuberculosis. Methods M. tuberculosis virulent strain （H37 Rv） that was cultured in the different levels of rifampicin and 36 isolated strains with the results of drug resistance were analyzed by polymerase chain reaction-single strand conformation polymorphism （PCR SSCP） and sequence analysis. Results The 7th generation of strain H37Rv had abnormal PCR-SSCP profile, was confirmed rpoB gene mutation at codon 513 hy DNA sequencing. Of 36 clinical isolates, 63.9% strains （23/36） had rpoB mutations. The mutation sites of 5 clinical isolates were the same as that of induced strains H37 Rv. Conclusions Stimulating constantly tubercle bacillus with rifampicin is an important reason that cause rifampicinresistant tuberculosis.