链霉蛋白酶对胃组织中治疗幽门螺杆菌药物浓度的影响  

The effects of pronase on drugs concentrations for treatment of Helicobacter pylori infection in gastric tissue

作　　者：田雪丽[1] 张建中[3] 周丽雅[1] 耿秋明[2] 韩亚京[1] 

机构地区：[1]北京大学第三医院消化科,100191 [2]北京大学第三医院中心实验室,100191 [3]中国疾病预防控制中心传染病所

出　　处：《中华内科杂志》2011年第7期604-607,共4页Chinese Journal of Internal Medicine

基　　金：国家科技支撑计划（2007BA104B02）

摘　　要：目的明确链霉蛋白酶应用对胃组织中阿莫西林和甲硝唑浓度的影响。方法C57BL／6小鼠随机分为实验组和对照组（每组70只），给予奥美拉唑（138．2mg／kg）＋阿莫西林（28．6mg／kg）＋甲硝唑（22．5mg／kg），并分别予链霉蛋白酶（110mg/kg）或等量的无菌PBS，上述药物灌胃1次，给药后15～360min共10个时间点（每组7只／时间点）取血浆和胃组织，高效液相色谱法检测阿莫西林和甲硝唑浓度，并检测给药后120、360min的胃组织黏膜层胃炎指数（HE法）和黏蛋白5AC的相对表达量（蛋白质印迹法）。结果阿莫西林和甲硝唑的胃组织浓度达峰时间早于在血浆出现的时间（均为15min比60min），实验组的胃组织浓度明显高于对照组（P〈0．05），主要集中在15～90min。实验组药物血浆浓度在15和30min较对照组高（P〈0．05）。给药后120、360min，实验组与对照组的胃黏膜层胃炎指数的差异均无统计学意义（0．28±0．18比0．14±0．14，P〉0．05；0．43±0．20比0．28±0．18，P〉0．05）；黏蛋白5AC的相对表达量实验组较对照组低（0．036±0．006比0．197±0．058，P〈0．05；0．039±0．008比0．208±0．072，P〈0．05）。结论链霉蛋白酶明显增加了抗菌药物从胃腔向胃黏膜方向的弥散量，使局部胃组织和血浆浓度升高，且以局部胃组织浓度升高为主，持续时间更长。Objective To evaluate the effect of pronase on amoxicillin and metronidazole concentrations in gastric tissue. Methods C57BL/6 mice were randomly divided into experimental group （ n = 70 ） and control group （ n = 70 ）. Amoxicillin （ 28.6 mg/kg ）, metronidazole （ 22. 5 mg/kg ） and omeprazole （138.2 mg/kg） were administered orally to C57BL/6 mice, combined with pronase （ll0 mg/kg） or same amount of sterile PBS. Gastric tissue and blood plasma samples were taken at 10 point-intime （7 mice/time） fi＇om 15 min up to 360 min after administration. Concentrations of amoxieillin and metronidazole were detected by high performance liquid chromatography. Gastritis index of gastric mucosa （hematoxylin-eosiu staining） and the gastric tissue expressions of muein 5AC （Western blot） were detected at 120 min and 360 min after administration. Results The time to peak concentration of amoxicillin and metronidazole in gastric tissue appeared earlier than that in blood plasma （15 min vs 60 min）. Tissue concentrations of amoxicillin and metronidazole of experimental group were significantly higher than those of control, and they were mainly at 15 min to 90 min （P 〈 0. 05）. Plasma concentrations of amoxicillin and metronidazole of experimental group at 15 rain and 30 rain were higher than those of control （ P 〈 0. 05 ）. There was no difference in gastritis index between experimental group and control at 120 min and 360 rain after administration （0. 28 ±0. 18 vs 0. 14 ± 0. 14, P 〉 0. 05 ; 0.43 ± 0. 20 vs 0. 28 ±0. 18, P 〉 0. 05 ）. The expressions of mucin SAC in experimental group were lower than those of control （ 0. 036±0. 006 vs 0. 197 ± 0. 058 ; P 〈 0. 05 ; 0. 039 ± 0. 008 vs 0. 208 ± 0. 072, P 〈 0. 05 ）. Conclusions Pronase can significantly enhance the drugs penetration from mucus into gastric tissue. Concentrations of amoxicillin and metronidazole of experimental group in local gastric tissue and plasma are higher than those of control, especially in imp

关 键 词：链霉蛋白酶 药物浓度 高效液相色谱法 黏蛋白5AC 

分 类 号：R573[医药卫生—消化系统]