Mitophagy-mtDNA-NLRP3介导的非可控性炎症促进口腔黏膜恶性转化的机制研究

非可控性炎症的预防及治疗是当前转化医学的研究热点。最新研究表明线粒体自噬（Mitophagy）障碍致mtDNA逃逸与多种非可控性炎症疾病密切相关。我们前期研究证实NLRP3炎症小体在口腔黏膜上皮恶性转化中起到重要作用。本项目进一步提出：Mitophagy-mtDNA-NLRP3共同介导了口腔黏膜上皮非可控性炎症的恶性转化。拟从三个方面研究：明确Mitophagy、mtDNA及NLRP3在口腔健康、癌前病损及癌变组织中的表达并进行分析；明确线粒体自噬障碍引起mtDNA逃逸并通过NLRP3调控口腔上皮恶性转化机制；通过动物模型的研究，明确Mitophagy、mtDNA、NLRP3作为口腔癌前病变诊断及治疗的可行性。本研究有望揭示Mitophagy-mtDNA-NLRP3调控非可控性炎症的新机制，为应用抗炎策略预防口腔黏膜上皮恶性转化的发生及治疗口腔癌提供理论依据。

The prevention and treatment of nonresolving inflammation are the hot topics in the field of translational medicine. Recent studies show that mitophagy is associated with a variety of nonresolving inflammatory diseases caused by mitophagy induced mtDNA release. Our previous study confirmed that the NLRP3 inflammasome plays an important role in the oral mucosa malignant transformation. We proposed that " mitophagy disorders cause mtDNA escape, and mtDNA escape activation of the NLRP3 inflammasome and mediated the malignant transformation of oral mucosa." Our objectives were as follows: To explore the expression of mitophagy, mtDNA and NLRP3 inflammasome in healthy, precancerous lesion and cancer tissues of oral mucosa; To explore the molecular mechanisms of mitophagy, mtDNA and the NLRP3 inflammasome in oral mucosal malignant transformation; To define whether mitophagy, mtDNA, the NLRP3 inflammasome may comprise effective targets for treatment of oral mucosal precancerous lesions by three animal models. This study is expected to reveal a new mechanism of Mitophagy-mtDNA-NLRP3 inflammasome regulating nonresolving inflammation, and provide theoretical and experimental basis for anti-inflammatory strategies to prevent the occurrence of oral mucosal malignant transformation and treat oral cancer.