Nakao M, Malfertheiner P
Pharmaceutical Research Laboratories III, Takeda Chemical Industries Ltd., Osaka, Japan.
Helicobacter. 1998 Mar;3(1):21-7. doi: 10.1046/j.1523-5378.1998.08024.x.
Helicobacter pylori plays a role in the pathogenesis of both duodenal and gastric ulcers. The aim of this study was to evaluate the effect of the proton pump inhibitor (PPI), lansoprazole, commonly used in eradication regimens, on growth, bactericidal activity and morphology of H. pylori in vitro in comparison with other PPIs.
Growth inhibitory activity of each of the PPIs was evaluated by determining minimum inhibitory concentrations using an agar dilution method. Bactericidal activity was determined by analysis of the viable cells in culture at various time points after incubation with different concentrations of the PPIs. Bacterial morphology was examined using scanning electron microscopy of fixed cells after exposure to the test substances. Urease activity in cell extracts of H. pylori that had been incubated with increasing concentrations of the PPIs was determined by colorimetry.
The growth inhibitory activity of lansoprazole was significantly more potent than that of omeprazole or pantoprazole (MIC90 6.25 vs. 25 and 100 micrograms/ml, respectively). Exposure of H. pylori to lansoprazole produced loss of viability and an aberrant bacterial morphology, which was more extensive than seen with omeprazole or pantoprazole. Lansoprazole dose dependently inhibited urease activity; its effectiveness was comparable with omeprazole but more potent than pantoprazole.
The mechanism of action that leads to loss of viability of H. pylori cells appears to differ between the three PPIs investigated; lansoprazole was the most potent of the three agents in terms of growth inhibition and disruption of bacterial morphology.
幽门螺杆菌在十二指肠溃疡和胃溃疡的发病机制中起作用。本研究的目的是评估根除方案中常用的质子泵抑制剂(PPI)兰索拉唑与其他PPI相比,对幽门螺杆菌体外生长、杀菌活性和形态的影响。
采用琼脂稀释法通过测定最低抑菌浓度评估每种PPI的生长抑制活性。通过分析与不同浓度PPI孵育后不同时间点培养物中的活细胞来确定杀菌活性。使用扫描电子显微镜检查暴露于测试物质后固定细胞的细菌形态。通过比色法测定与浓度递增的PPI孵育后的幽门螺杆菌细胞提取物中的脲酶活性。
兰索拉唑的生长抑制活性明显强于奥美拉唑或泮托拉唑(MIC90分别为6.25 vs. 25和100微克/毫升)。幽门螺杆菌暴露于兰索拉唑会导致活力丧失和细菌形态异常,这种情况比奥美拉唑或泮托拉唑更广泛。兰索拉唑剂量依赖性地抑制脲酶活性;其有效性与奥美拉唑相当,但比泮托拉唑更强。
在所研究的三种PPI中,导致幽门螺杆菌细胞活力丧失的作用机制似乎有所不同;就生长抑制和细菌形态破坏而言,兰索拉唑是三种药物中最有效的。