味觉受体基因多态性与糖尿病患者牙周炎易感性的关联及分子机制研究

Patients with diabetes are more vulnerable to periodontitis than those with normal glycaemia, which poses a serious threat to the oral function, and control of diabetes and its complications. Mechanisms leading to diabetic patients’ increasing susceptibility to periodontitis are still not clear yet. By using the most common clinical manifestations of diabetes (i.e., diabetic hyperglycemia), the newly discovered innate immune member (i.e., taste receptors ) and initiating factor of periodontitis (i.e., subgingival microbiota ) as starting points, and in vitro experiments, animal model, and clinic survey as carriers, this proposal will identify the effect of bitter taste receptors T2R activation on periodontal microflora, and the interference of sweet receptors T1R2/R3 activated by diabetic hyperglycemia on the periodontal protection of T2R through cytological, molecular biological, microbiological, animal and high throughput metagenomic technologies. Furthermore, the association between taste receptor gene polymorphisms and periodontitis susceptibility of diabetes will be analyzed deeply. Such effort will provide new ideas and therapeutic targets for the prevention and treatment of periodontitis in patients with diabetes.

糖尿病患者可表现出较血糖正常者更高的牙周炎易感性，严重影响口腔局部功能、糖尿病及糖尿病并发症的控制。迄今为止，糖尿病患者牙周炎易感的机制尚不明确。本研究以糖尿病的基本临床表现（高血糖）、最新发现的机体固有免疫成员（味觉受体）及牙周炎的始动因素（牙周龈下菌群）为切入点，以体外实验、动物模型、人群调查为载体，依托细胞学技术、分子生物学技术、微生物学技术、实验动物技术及高通量宏基因组学技术，拟研究苦味受体T2R在牙周微生态中的菌群调节作用、探索糖尿病高血糖状态激活甜味受体T1R2/R3后对T2R菌群调节功能的干扰、在此基础上进一步分析甜味及苦味受体基因多态性与糖尿病患者牙周炎易感性之间的关联并揭示该关联潜在的分子机制，为糖尿病患者牙周炎的预防及治疗提供新的思路及治疗靶点。

味觉受体是哺乳动物舌部的味觉终端感受器。近年来研究发现，味觉受体可表达于舌外组织，利用经典味觉信号通路识别细菌代谢产物，参与固有免疫反应。然而，味觉受体在口腔内非舌体组织的分布及作用尚不清楚，在常见口腔感染性疾病的发生发展中的作用亟待明确。本项目在国家自然基金的资助下，确定了味觉受体（包括苦味受体T2R及甜味受体T1R）及介导其信号通路的重要分子在小鼠牙周组织中原位表达情况；通过转基因动物体内实验证实了味觉受体介导的信号通路调节了小鼠龈下菌群、参与了牙周炎的发生发展；并垂钓了相关机制。在此基础上，进一步确定了味觉受体（包括苦味受体T2R及甜味受体T1R）信号通路在人牙周组织中的表达情况及编码基因的多态性，并通过体外实验证实了人牙周组织细胞表达的苦味受体具有介导信号通路活化、参与牙周固有免疫反应的功能。本项目的研究为口腔感染性疾病的的预防及治疗提供新的思路及治疗靶点。