Dattilo M, Figura N
ICN Pharmaceuticals, Medical Research Division, Rome, Italy.
J Clin Gastroenterol. 1998;27 Suppl 1:S163-9. doi: 10.1097/00004836-199800001-00027.
The proton pump inhibitors (PPIs) omeprazole, lansoprazole, and pantoprazole are widely used as antisecretory drugs and, in association with antibiotics, for the treatment of Helicobacter pylori infections. PPIs possess antibacterial activity against H. pylori in vitro, and may also exert an anti-inflammatory effect by interfering with the cellular immune response to infection. Their antimicrobial activity is selective for H. pylori. Lansoprazole is the most effective, although its bactericidal activity is similar to that of omeprazole. Pantoprazole is the least effective. The mechanisms that account for the antibacterial effects of PPIs may depend on a structural similarity of PPIs to antibiotics which are active against H. pylori, on the inhibition of bacterial urease exerted by PPIs, or on the possible interaction of PPIs with bacterial ATPases that regulate the transmembrane ion flux. Recent studies have shown that PPIs have anti-inflammatory actions and can interfere with the host-bacteria interactions. Lansoprazole can bind to polymorphonuclear leukocytes that infiltrate the gastric mucosa colonized by H. pylori and can thus inhibit the oxidative burst of activated inflammatory cells. In an in vivo study, lansoprazole reduced the degree of activity of histologic gastritis independently of the presence of H. pylori. In another study, omeprazole was capable of inhibiting the cytotoxic activity of NK T cells. Investigation of PPI interactions with H. pylori activities and the cellular immune response to the infection may help us to understand the pathogenic mechanisms of H. pylori-associated diseases and enable clinicians to better treat them.
质子泵抑制剂(PPIs)奥美拉唑、兰索拉唑和泮托拉唑被广泛用作抗分泌药物,并与抗生素联合用于治疗幽门螺杆菌感染。PPIs在体外对幽门螺杆菌具有抗菌活性,还可能通过干扰对感染的细胞免疫反应发挥抗炎作用。它们的抗菌活性对幽门螺杆菌具有选择性。兰索拉唑最为有效,尽管其杀菌活性与奥美拉唑相似。泮托拉唑效果最差。PPIs抗菌作用的机制可能取决于PPIs与对幽门螺杆菌有活性的抗生素的结构相似性、PPIs对细菌尿素酶的抑制作用,或PPIs与调节跨膜离子通量的细菌ATP酶的可能相互作用。最近的研究表明,PPIs具有抗炎作用,可干扰宿主与细菌的相互作用。兰索拉唑可与浸润幽门螺杆菌定植的胃黏膜的多形核白细胞结合,从而抑制活化炎症细胞的氧化爆发。在一项体内研究中,兰索拉唑降低了组织学胃炎的活动程度,与幽门螺杆菌的存在无关。在另一项研究中,奥美拉唑能够抑制NK T细胞的细胞毒活性。研究PPIs与幽门螺杆菌活性及对感染的细胞免疫反应之间的相互作用,可能有助于我们理解幽门螺杆菌相关疾病的致病机制,并使临床医生能够更好地治疗这些疾病。