奥美拉唑对耐药幽门螺杆菌的抗菌作用及机制探讨

Activity and mechanism of omeprazole against resistantstrains of Helicobacter pylori

目的 探讨质子泵抑制剂奥美拉唑对耐药幽门螺杆菌（Ｈｐ） 的抗菌作用及机制。方法以药物梯度平皿筛选得到耐甲硝唑的Ｈｐ 菌株，采用试管肉汤二倍稀释法、Ｂａｚｅｌ’ｓ 法和间接酶联免疫吸附法（ＥＬＩＳＡ） 等测定奥美拉唑对Ｈｐ 的最低抑菌浓度（ＭＩＣ） 及对Ｈｐ ＡＴＰ酶活性和Ｈｐ 积聚甲硝唑的影响。结果 （１） 奥美拉唑对甲硝唑耐药Ｈｐ 菌的ＭＩＣ 为１．６０μｇ／ｍｌ～６ ．２５μｇ／ｍｌ，在耐药菌中加入奥美拉唑和甲硝唑可几乎完全抑制Ｈｐ 的生长；（２） 奥美拉唑组Ｈｐ 的ＡＴＰ 酶活性显著低于对照组（ Ｐ＜０．００１） ，Ｉ５０（抑制５０ ％ ＡＴＰ酶活性所需奥美拉唑浓度）为０．８０μｇ／ｍｌ～３．１３μｇ／ｍｌ；（３） 奥美拉唑组的Ｈｐ菌体内甲硝唑的浓度显著高于对照组（ Ｐ＜ ０．００１）。结论 奥美拉唑对甲硝唑耐药Ｈｐ 菌有良好的体外抗菌活性，能改善Ｈｐ 耐药株对甲硝唑的敏感性，其机制可能与奥美拉唑抑制Ｈｐ 的ＡＴＰ酶活性，增加药物在菌体内的积聚有关。

Objective To studytheactivity ofomeprazoleagainstresistantstrains of Helicobacter py lori(Hp) andits mechanism . Methods Hp wassubjectedtoaserialpassagetechniqueto developresistanceto metronidazole. Minimum inhibitory concentration (MIC) of Hpto omeprazole was determined bytube broth double dilution method.Theinfluenceofomeprazole on ATPase activitiy of Hp was observed.The effectof omeprazoleon accumulation of metronidazolein strainsof Hp wasstudied using ELISA.Results the MICof resistantstrainsof Hpto omeprazole was1.60μg/ml- 6.25μg/ml.Thegrowth ofresistantstrainsof Hp canbecompletelyinhibited by omeprazole with metronidazole.In omeprazole group,the ATP ase activitiy of Hp wassignificantly decreased ascompared with thatofcontrols (P< 0.001) .I50(theconcentration ofomepra zolerequired tocause50% inhibition ofthe ATPase activitiy) was0.8μg/ml- 3.125μg/ml.Theconcentra tion of metronidazole in Hp was significantly increased after adding omeprazole ( P< 0 .001) .Conclusions omeprazole hasstrong activity againstresistantstrains of Hpin vitro and canimprovethesensitivity of Hp to metronidazole.The mechanism ofthisphenomenon may be duetoinhibition of ATPase,increaseoftheaccu mulation of drugin the Hp .