肌成纤维细胞及其抗凋亡能力在颌骨放射性骨坏死发病机制中作用的实验研究

项目名称： 肌成纤维细胞及其抗凋亡能力在颌骨放射性骨坏死发病机制中作用的实验研究

项目编号： No.81202150

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 田磊

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 放射性颌骨坏死（ORNJ）是头颈部恶性肿瘤患者放疗后常见且难治的并发症，严重影响生存质量。ORNJ的发病机制尚不明瞭，至今仍缺乏针对ORNJ非常有效的预防和治疗措施，此领域也一直是国内外研究热点。最新的放射性纤维萎缩假说认为ORNJ本质是一种放射性纤维化，而临床应用抗纤维化药物治疗也取得了明显的疗效，但缺乏实验依据和深入研究。我们以纤维化疾病中的主要效应细胞―肌成纤维细胞(myofibroblast，MFB)为切入点，通过建立ORNJ动物模型，培养MFB细胞并观察其细胞来源、分化和转归；研究TGF-β1对MFB分化的调控作用及Fas/FasL途径在MFB获得抗凋亡能力中的作用；最后应用TGF-β1和FasL的中和抗体及肝细胞生长因子进行体外体内干预实验，观察抑制MFB转化和促其凋亡是否可以改善和逆转动物的ORNJ，以期部分阐明ORNJ的发病机制，为探索预防和治疗的新方法提供理论依据。

中文关键词： 放射性骨坏死；下颌骨；肌成纤维细胞；转化生长因子β1；放射性纤维化

英文摘要： Osteoradionecrosis of jaws (ORNJ) is the most devastating long-term complication of radiotherapy in the head and neck area with slow progress and does not tend to heal spontaneously， which is very harmful for the patients quality of life. However, the precise pathogenesis of ORNJ has not been fully clarified yet. Many theories about how ORNJ occurs have been formulated and each has led sequential treatment protocol in past 90 years, but all of them have been proved to be obviously defective. The etiopathogenesis of ORNJ are still not consensual, which also makes obstacles to the prevention and management of ORNJ. And relative research has been the hotspot for the clinicians and pathologists. In recent years, a new theory for the pathogenesis of ORNJ has arisen and indicated ORNJ to be the radiation induced fibroatrophic disease, and some anti-fibrosis medicine, Pentoxifylline and Tocopherol, for example, have been applied to treat ORNJ and proved dramatical outcome. Despite its clinical effectiveness, this theory needs deeper study and experimental support. Therefore, we focus on the myofibroblast(MFB), the key effector cell in all fibrosis diseases, and assumed that ORNJ, like fibrosis in all other organs, is the result of a process of fibrogenesis. We are going to establish an animal model for ORNJ, then test

英文关键词： osteoradionecrosis；mandible；myofibroblasts；transforming growth factor β1；radiation-induced fibrosis