自噬对牙周炎微环境中牙周膜干细胞凋亡的调控及机制研究

Periodontitis cause the decrease survival ability and apoptosis of periodontal ligament stem cells (PDLSCs), and strongly influence the repair and regeneration of the periodontal tissue. Autophagy play a key role in regulating cell function and maintain the body homeostasis. Our previous study found that autophagy play a protective effect on the process of apoptosis caused by periodontitis in PDLSCs. However, the regulate role between autophagy and apoptosis of PDLSCs and the mechanism is not yet fully understood. Based on this research, we intend to simulate the inflammatory microenvironment by inflammatory factor which was screened in vitro, investigate the influence of inflammatory microenvironment on autophagy and apoptosis of PDLSCs and the mechanism of autophagy regulate the apoptosis of PDLSCs in periodontitis by transmission electron microscopy, immunofluorescence and western blot, further to illustrate the role and its molecular mechanism of autophagy in apoptosis of stem cells. Our research not only provides a theoretical basis for improving the regeneration ability of stem cells through changing the level of autophagy under inflammatory microenvironment, but also offers a good method for enhancing the survival rate of MSCs in cell transplantation for clinical application. Moreover, our research further improved the mechanism of autophagy and apoptosis.

牙周炎微环境导致牙周膜干细胞（PDLSCs）生存能力下降，继而发生凋亡，严重影响牙周组织的修复与再生。自噬在细胞功能的调控方面发挥着重要作用，通过本课题组前期研究，发现自噬在牙周炎引起的PDLSCs凋亡过程中具有保护作用，但是自噬是如何调控PDLSCs的凋亡及相关机制尚不明确。因此，本课题拟利用筛选的炎性因子模拟炎症微环境，采用透射电子显微镜、免疫荧光染色和蛋白印迹等分子生物学手段检测炎症微环境下PDLSCs自噬和凋亡的变化，着重探讨自噬对牙周炎微环境中PDLSCs凋亡水平的调控及分子机制等内容，并阐明自噬对干细胞凋亡的影响及相关分子机制。本研究不仅为基于改变自噬水平来提升炎症微环境下细胞的再生能力提供了理论依据，而且为提高临床应用干细胞移植的成活率给予重要的借鉴意义，并进一步完善了自噬与凋亡的作用机制理论。

牙周炎微环境导致牙周膜干细胞（PDLSCs）生存能力下降，继而发生凋亡，严重影响牙周组织的修复与再生。自噬在细胞功能的调控方面发挥着重要作用，通过本课题组前期研究，发现自噬在牙周炎引起的PDLSCs凋亡过程中具有保护作用，但是自噬是如何调控PDLSCs的凋亡及相关机制尚不明确。因此，本课题拟利用筛选的炎性因子模拟炎症微环境，采用透射电子显微镜、免疫荧光染色和蛋白印迹等分子生物学手段检测炎症微环境下PDLSCs自噬和凋亡的变化，着重探讨自噬对牙周炎微环境中PDLSCs凋亡水平的调控及分子机制等内容，发现炎症微环境刺激PDLSCs的自噬水平升高，并发现自噬可以通过P-ERK通路调控MSCs的旁分泌功能，进而加速内皮细胞的血管化，促进组织的愈合。本研究不仅为基于改变自噬水平来提升炎症微环境下细胞的再生能力提供了理论依据，而且为提高临床应用干细胞移植的成活率给予重要的借鉴意义，并进一步完善了自噬调控干细胞功能的作用机制理论。