胰岛素局部给药对糖尿病人工种植体骨结合的作用及机理研究

To improve the success ratio of dental implant for patients with tooth loss accompanied with diabetes is a difficulty but research hot topic in the dental implant field, and the key is to enhance implant osteointegration.Previous studies have showed that the effect of improving implant osteointegration by systemic adminstration of hypoglycemic drug such as insulin and metformin is very limited .Recently, several clinical study found that implant osteintegration could be significantly enhanced by local adminstration of insulin. However, the mechanism is still unclear and also few study is done by now. Based on our previous researches which demonstrate that a high glucose environment could reduce the susceptibility of mandibular osteoblasts to insulin, and hypoglycemic drug may regulate the function of osteoblasts by PI3 kinase/ Akt signal pathway,the present study will further investigate the molecular mechanism of insulin administrated locally mediated by osteoblasts on implant osteointegration of diabetes type II, and the mechanism and the key steps of insulin in controlling the function of osteoblasts by PI3 kinase/Akt signal pathway during drug administrated locally. The aim of this study is to elucidate the melocular mechanism of insulin administrated locally in promoting osteogensis of osteoblasts at gene control and signal transduction levels, and subsequently, to determine their effects in model animal. As a result, a useful way will be found to evaluate the efficicy, safety and proper dose of hypoglycemic drug administrated locally for enhancing implant osteointegration and a scitific guidance will be made for their clinical application. This study may provide a theoretical basis for local adiminstration of insulin in improving implant osteointegration and also provide new way for resolving the throny problem of dental implant applicating in patients with tooth loss in combination with diabetes.

提高糖尿病缺牙患者人工种植牙修复成功率是目前种植牙领域亟待解决的难题，改善种植体骨结合是关键。既往全身给予降糖药对改善局部种植体骨结合作用有限，临床发现种植体局部应用胰岛素能提高种植体骨结合率，但作用机理不明确，也较少报道。本课题在前期研究发现高糖可致下颌骨成骨细胞对胰岛素敏感性下降及降糖药通过PI3 kinase/ Akt 通路影响成骨细胞功能基础上，采用分子生物学方法，进一步探讨胰岛素局部给药对糖尿病人工种植牙周成骨细胞功能、种植体骨结合的影响及局部应用胰岛素等对颌骨成骨细胞骨形成通路PI3 kinase/ Akt 调控的关键环节及相互作用，从基因调控和信号通路水平阐明胰岛素局部给药影响成骨细胞骨形成的分子机理，并在模型动物上检测其应用效果。探寻局部给药促进种植体骨结合的有效性、安全性及适宜剂量。本研究为糖尿病人工种植牙局部应用胰岛素促进种植体骨结合提供科学依据和临床指导。

提高糖尿病缺牙患者人工种植牙修复成功率是目前种植牙领域亟待解决的难题，改善种植体骨结合是关键。既往全身给予降糖药对改善局部种植体骨结合作用有限，临床发现种植体局部应用胰岛素能提高种植体骨结合率，但作用机理不明确，也较少报道。本课题在前期研究发现高糖可致下颌骨成骨细胞对胰岛素敏感性下降及降糖药通过PI3 kinase/ Akt 通路影响成骨细胞功能基础上，采用分子生物学方法，进一步探讨胰岛素局部给药对糖尿病人工种植牙周成骨细胞功能、种植体骨结合的影响及局部应用胰岛素等对颌骨成骨细胞骨形成通路PI3 kinase/ Akt 调控的关键环节及相互作用，从基因调控和信号通路水平阐明胰岛素局部给药影响成骨细胞骨形成的分子机理，并在模型动物以及临床病人检测其应用效果。探寻局部给药促进种植体骨结合的有效性、安全性及适宜剂量。本研究为糖尿病人工种植牙局部应用胰岛素促进种植体骨结合提供科学依据和临床指导。