Wang W H, Wong W M, Dailidiene D, Berg D E, Gu Q, Lai K C, Lam S K, Wong B C Y
Department of Gastroenterology, First Hospital, Peking University, Beijing, China.
Gut. 2003 Apr;52(4):490-5. doi: 10.1136/gut.52.4.490.
The role of Helicobacter pylori and aspirin in peptic ulcer formation and recurrence remains an important clinical topic. The interaction between aspirin and H pylori in vitro is also not clear. We investigated the effect of aspirin on the growth of H pylori and on the susceptibility of H pylori to antimicrobials.
Time killing studies of H pylori were performed with different concentrations of aspirin and salicylate. Growth of bacteria was assessed spectrophotometrically and by viable colony count. The effects of aspirin on the efficiency of colony formation and on metronidazole induced mutation to rifampicin resistance in H pylori were determined. Minimal inhibitory concentrations (MICs) of aspirin and metronidazole were tested by the standard agar dilution method. MICs of amoxycillin and clarithromycin were determined by the E test method.
Aspirin and salicylate inhibited the growth of H pylori in a dose dependent manner and bactericidal activity was due to cell lysis. Aspirin 400 micro g/ml caused a 2 logs decrease in colony forming units/ml at 48 hours, and suppressed the normal ability of metronidazole to induce new mutations to rifampicin. The IC(90) of aspirin was 512 micro g/ml. Increased susceptibility of amoxycillin, clarithromycin, and metronidazole to H pylori was observed at 1 mM (180 micro g/ml) aspirin.
Aspirin inhibited the growth of H pylori, suppressed the mutagenic effect of metronidazole, and enhanced the susceptibility of H pylori to antimicrobial agents. This mechanism is important in future drug development for effective clearing and overcoming resistance.
幽门螺杆菌和阿司匹林在消化性溃疡形成及复发中的作用仍是一个重要的临床课题。阿司匹林与幽门螺杆菌在体外的相互作用也尚不清楚。我们研究了阿司匹林对幽门螺杆菌生长及对其对抗菌药物敏感性的影响。
用不同浓度的阿司匹林和水杨酸盐进行幽门螺杆菌的时间杀菌研究。通过分光光度法和活菌菌落计数评估细菌生长。测定阿司匹林对幽门螺杆菌菌落形成效率及对甲硝唑诱导的对利福平耐药突变的影响。采用标准琼脂稀释法检测阿司匹林和甲硝唑的最低抑菌浓度(MIC)。采用E试验法测定阿莫西林和克拉霉素的MIC。
阿司匹林和水杨酸盐以剂量依赖方式抑制幽门螺杆菌生长,杀菌活性归因于细胞裂解。400μg/ml的阿司匹林在48小时时使每毫升菌落形成单位减少2个对数,并抑制了甲硝唑诱导利福平新突变的正常能力。阿司匹林的IC90为512μg/ml。在1mM(180μg/ml)阿司匹林存在时,观察到阿莫西林、克拉霉素和甲硝唑对幽门螺杆菌的敏感性增加。
阿司匹林抑制幽门螺杆菌生长,抑制甲硝唑的诱变作用,并增强幽门螺杆菌对抗菌药物的敏感性。这一机制在未来有效清除和克服耐药性的药物研发中具有重要意义。