利血平对耐药结核分枝杆菌临床株的作用

Effects of Reserpine on the Drug-Resistant Mycobacterium tuberculosis

目的观察泵抑制剂(利血平)对耐药结核分枝杆菌临床分离株的作用。方法应用3组BacT.ALERT3D培养仪系统的培养基,分别命名为A、B、C组培养基。3组培养基均接种42株耐药结核分枝杆菌临床分离株,其中A、B组同时加入利福平1μg/mL;环丙沙星2μg/mL;利福平1μg/mL和环丙沙星2μg/mL;A、C组同时加入利血平20mg/L;C组未加入任何抗结核药物。结果在A组培养基中,耐利福平1μg/mL的14株菌株中有2株恢复对利福平的敏感性,12株仍然耐药;耐环丙沙星2μg/mL的6株菌株和耐利福平1μg/mL及环丙沙星2μg/mL的22株菌株全部恢复药物敏感性。在B组培养基中,42株耐药结核分枝杆菌临床分离株,药物耐药性无变化。在C组培养基中,42株耐药结核分枝杆菌临床分离株明显生长,说明利血平对所研究菌株无抑制作用。A组与B组培养基细菌的药物敏感性差异有统计学意义(P<0.01)。结论结核分枝杆菌存在耐药机制之一的外排系统;泵抑制剂之一利血平对耐药的结核分枝杆菌临床分离株有抑制其外排作用,使结核分枝杆菌恢复敏感性。

Objective To determine the antibacterial activities of an efflux pump inhibitor reserpine on the clinical isolates of drug-resistant Mycobacterium tuberculosis. Method BacT/ALERT3D was used in this study. 3 groups of culture plates （A, B, and C） were setup. 42 clinical isolates of M.tuberculosis were inoculated into group A, B, and C. Rifampicin （1 μg/mL）, Ciprofloxacin （2 μg/mL）, Rifampicin （1 μg/mL）, and Ciprofloxacin （2 μg/mL） were added to both group A and group B. Reserpine （20 mg/L） was added to both A and C. Group C did not receive anti-tuberculosis drug. Result 2 of the 14 Rifampicin-resistant isolates were found to be sensitive to Rifampicin. All 6 Ciprofloxacin-resistant isolates and 22 both Ciprofloxacin- and Rifampicin-resistant isolates were found to be sensitive for the two drugs in A group. In group B, changes of drug sensitivity were not observed in all 42 isolates. In group C, the growth of all 42 isolates were similar, indicating that reserpine had no growth inhibitory effect on these isolates. A significant difference was found in the drug sensitivity between group A and group B （P 〈 0.01）. Conclusion The efflux pump inhibitor reserpine can inhibit the drug efflux system of drug-resistant Mycobacterium tuberculosis and restores the drug sensitive of the bacteria to anti-tuberculosis drugs.