靶点灌注臭氧治疗慢性骨髓炎的实验研究

项目名称： 靶点灌注臭氧治疗慢性骨髓炎的实验研究

项目编号： No.81201415

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 毛宁方

作者单位： 中国人民解放军第二军医大学

项目金额： 23万元

中文摘要： 慢性骨髓炎是医学界公认的顽症之一，病灶内游离态抗菌药物浓度不足导致治愈率低和复发率高等问题始终未能彻底解决。臭氧是一种强氧化剂，具有广谱高效杀菌作用，近年来的实验研究表明，适当浓度的臭氧还具有杀灭细菌生物膜、调节机体氧化应激、改善组织微循环等作用。我们前期实验中已发现，慢性骨髓炎动物模型病灶局部经臭氧灌注后，骨组织间液游离抗菌药物浓度高于对照组。本课题首先建立靶点灌注臭氧治疗兔胫骨慢性骨髓炎模型，利用微透析取样技术对靶组织抗菌药物的药代动力学进行研究，探讨臭氧与抗菌药物的协同作用关系；其次，通过测定靶组织IL-1、IL-10、TNF-α的含量及MDA、SOD、GSH-Px活性，并通过影像学、病理学和微生物学手段评估疗效，摸索出臭氧局部治疗的有效方案。通过本实验研究，我们试图阐明局部应用臭氧治疗慢性骨髓炎的内在作用机制，从而为慢性骨髓炎的治疗开辟新思路与新途径。

中文关键词： 盐酸万古霉素；微透析；药代动力学；药效学；臭氧

英文摘要： Chronic osteomyelitis is generally treated with antibiotics and surgical debridement but can persist intermittently for years with frequent therapeutic failure. One of the possible reasons for failure may be a limited concentration of antimicrobial drugs in the infected target. Ozone is one of the most potent oxidants. In light of newer pharmacologic knowledge, some authors have considered ozone as apro-drug which, at certain nontoxic doses, can induce a rearrangement of the biochemical pathways with the activation of a second messenger in a cascade with a multisystem action. In our prior experiment, we found that unbound antibiotic concentration at infected bone tissue in the group treated with ozone got higher value than that in the controll group in an experimental rabbit model of chronic osteomyelitis. In further study, We aimed at studying the pharmacokinetic profile of antibiotic at target site through a model of chronic osteomyelitis treated with ozone, which was established in rabbit. Moreover, we would validate the efficacy of ozone therapy using oxidative stress parameters (MDA, SOD, GSH-Px), inflammatory cytokines (IL-1、IL-10、TNF-α), histopathological and microbiologic analyses. We would also describe the mechanisms of action involved in ozone therapy, and new adjuvant treatment would therefor be eval

英文关键词： vancomycin；microdialysis；pharmacokinetics；pharmacodynamics；ozone