C反应蛋白通过下调IRS-2信号介导牙周炎加重糖尿病的机制研究

Periodontitis has a negative impact on metabolic level in patients with diabetes. However, mechanism for effects of chronic periodontitis on diabetes remains unclear. Our previous researches have found that chronic periodontitis was associated with glyemic metabolic and serum C reactive protein (CRP) levels in patients with type 2 diabetes; non-surgical periodontal treatment can effectively reduce serum CRP level, improve circulating inflammatory and metabolic status; there is a high reliability of positive linear correlation between circulating CRP level and insulin resistance index in rats; periodontitis may exacerbate insulin resistance in obesity rats by lowering insulin receptor substrate-2（IRS-2）which is a key protein insulin signaling pathway. This project aims to explore molecular mechanism of CRP playing in the effects of periodontitis on diabetes in rats, targeting IRS-2. And this project helps to improve public attention of periodontal health and provides new ideas and theoretical basis for delaying the development of diabetes complications.

牙周炎对糖尿病代谢控制具有负面影响，但相关机制的研究却极少，具体作用机理尚不明确。本课题小组前期研究已证实牙周炎的严重程度与血清C反应蛋白（CRP）浓度和糖代谢水平正相关；牙周基础治疗能够有效降低CRP水平，改善2型糖尿病患者机体炎症状态和代谢水平；动物模型初步证明大鼠血清CRP水平与胰岛素抵抗指数高度线性正相关；牙周炎可能通过下调胰岛素受体底物-2 （IRS-2）途径，加重大鼠胰岛素抵抗。在前期研究的基础上，本项目通过建立糖尿病牙周炎大鼠模型和体外培养大鼠肝脏细胞，以胰岛素信号传导通路上关键蛋白IRS-2为切入点，探讨CRP在牙周炎影响糖尿病中发挥的作用，初步阐明CRP在牙周炎促进糖尿病发生发展中发挥致病作用的分子机理。本项目对于提升大众对牙周健康的重视，对于糖尿病的有效治疗具有一定临床指导价值，为延缓糖尿病的发展和并发症的发生提供新思路和理论依据。

牙周炎对糖尿病代谢控制具有负面影响，但相关机制的研究却极少，具体作用机理尚不明确。本项目利用高脂饮食喂养SD大鼠成功建立肥胖的2型糖尿病前期复合牙周炎大鼠模型，探讨实验性牙周炎和牙周非手术治疗对肥胖的2型糖尿病前期复合牙周炎大鼠炎症指标、胰岛素抵抗等全身代谢水平的影响。研究结果显示：1.实验性牙周炎会加重肥胖大鼠的胰岛素抵抗状态并下调β细胞功能；实验性牙周炎影响肥胖大鼠血清CRP、空腹血糖水平；2.牙周非手术治疗可以下调肥胖复合牙周炎大鼠的CRP水平，改善肥胖大鼠的糖代谢状况。3.牙周炎可促进肥胖大鼠的胰岛素抵抗水平及肝脏胰岛素受体底物IRS-2表达降低、FAT/CD36表达升高。牙周非手术治疗对肥胖合并牙周炎大鼠胰岛素抵抗有改善作用，同时也可升高肝脏IRS-2表达、降低FAT/CD36的表达。本项目结果显示局部牙周炎影响全身系统健康，牙周治疗改善全身代谢水平，为糖尿病的防空提供的临床指导价值，为延缓糖尿病的发展和并发症的发生提供新思路和理论依据。