Th17细胞作为牙龈卟啉单胞菌感染免疫应答的参与者与ApoE-/-小鼠动脉粥样硬化进展的相关研究

Periodontitis is a chronic inflammatory disease induced by subgingivial infection with large variety of gram-negative anaerobic bacteria for the destruction of the tooth supporting tissues, and it is a major cause of tooth loss. Atherosclerosis is a multifactor cardiovascular disease, and is a leading cause of high mortality and morbidity. Many studies have reported an association between periodontitis and cardiovascular disease. It has been shown that Porphyromonas gingivalis as an important pathogen not only caused periodontitis but also associated with the development of atherosclerosis. Those two diseases were linked and affected by the host inflammatory and immune responses as important factors according to the infection. T cells secrets inflammatory cytokines are major in regulating immune responses during the development of atherosclerosis. Th17 cells are new T subsets that have been implicated to play a central role in chronic inflammatory diseases, and may promote the development of atherosclerosis in recent studies. So our topic is basing on the protein and gene levels with immunology view to investigate the variations and trends of Th17 cells related inflammatory cytokines, and the interaction with other T cell subsets from ApoE-/- mice intravenously infected by Porphyromonas gingivalis. We will analysis the mechanism of those factors which induce the development of atherosclerosis, and then interfere the key biomarker of cytokine IL-17 to finding a new way for reducing the risk of cardiovascular disease.

牙周病是由龈下大量革兰氏阴性厌氧菌引起牙齿支持组织破坏，导致牙齿缺失的一种慢性炎症疾病。动脉粥样硬化是由多种因素引起，具有较高死亡率和发病率的心血管疾病。许多研究报告表明牙周病与心血管疾病有一定的关联性，牙龈卟啉单胞菌作为重要的病原体，不仅会导致牙周炎也与动脉粥样硬化的进展有关。经其感染，宿主的炎症和免疫应答反应成为连接和影响上述疾病的重要因素。在动脉粥样硬化发展过程中，T细胞分泌细胞因子，参与机体免疫应答的调节。近来有研究表明T细胞新亚型Th17在慢性炎症性疾病中发挥重要作用，可能促进动脉粥样硬化病变的进展。因此本课题通过ApoE-/-小鼠模型经尾静脉感染牙龈卟啉单胞菌后，从蛋白水平、基因水平及免疫学角度观察Th17细胞相关炎症细胞因子的变化趋势，与其它T细胞亚群的相互作用，分析其诱导动脉粥样硬化发展的机制，对于关键性细胞因子IL-17实施干预措施，探索降低心血管疾病致病风险的新途径。

牙周病是由龈下大量革兰氏阴性厌氧菌引起牙齿支持组织破坏，导致牙齿缺失的一种慢性炎症疾病。许多研究报告表明牙周病与心血管疾病有一定的关联性，牙龈卟啉单胞菌作为重要的病原体，不仅会导致牙周炎也与动脉粥样硬化的进展有关。经其感染，宿主的炎症和免疫应答反应成为连接和影响上述疾病的重要因素。在动脉粥样硬化发展过程中，T细胞分泌细胞因子，参与机体免疫应答的调节。尽管Th1细胞与心血管疾病的免疫应答反应的调控有关，近来有研究表明T细胞新亚型Th17在慢性炎症性疾病中发挥重要作用，可能促进动脉粥样硬化病变的进展。此外Treg细胞可以通过抗炎效果调控Th1/Th17细胞的表达，但牙龈卟啉单胞菌的感染仍然加速动脉粥样硬化的进展。每五只ApoE基因敲除的小鼠为一组经尾静脉感染牙龈卟啉单胞菌，每周三次共计三周，然后分别在感染后1周、3周和5周后处死小鼠。邻近主动脉的病变区通过油红染色检测，脾细胞培养液通过流式细胞技术和细胞因子ELISA检测 IL-17, IL-10和IFN-γ的表达水平，此外Th1/Th17/Treg相关因子的表达通过实时荧光定量PCR测定。因此本研究表明感染牙龈卟啉单胞菌后动脉粥样硬化的进展是IL-17与IFN-γ共同作用的结果。