Nrf2通路对齿科单体及抗菌粘接剂细胞毒性的拮抗作用研究

Preservation of the pulp is a common goal for dentists. However, successful preservation of the pulp in deep caries is difficult in clinical practice. Antibacterial adhesives containing quaternary ammonium monomers have good sealing properties and stable bactericidal/bacteristatic effects, and thus is recognized as promising materials for pulp preservation in deep caries. However, the negative influences of various monomers contained in antibacterial adhesives on the pulp tissue may compromise the outcome of treatment using antibacterial adhesives. In our previous work, it was found that dental monomers are strong electrophilic agents and can induce cytotoxic effects through oxidative stress. The Nrf2 pathway is a key element in the defending system against electrophilic and oxidative stress. Therefore, up-regulation of the Nrf2 pathway may protect the cells against dental monomer-related cytotoxicity. Based on the previous research results of our group, the present project aims to elucidate the influences of dental monomers on the intracellulae Nrf2 pathway and investigate the changes in the susceptibility of cells to the cytotoxic effects of dental monomers after modification of the Nrf2 expression. Furthermore, we will also explore whether the natural polyphenol agent procyanidin could up-regulate the Nrf2 pathway and protect the cells against the cytotoxicity of dental monomers and antibacterial adhesives. This research will assist to elucidate the defending effects of the Nrf2 pathway against the cytotoxicic effects of dental monomers and provide theoretical and experimental support for the searching of effective strategies to improve the prognosis of pulp preservation in deep caries using antibacterial adhesives.

保存活髓是口腔医生追求的共同目标，但深龋患牙的活髓保存成功率低，是临床亟待解决的问题之一。含季铵盐单体的抗菌粘接剂具有良好的封闭及抗菌性能，为深龋的保髓治疗提供了新的选择，但其所含的各类单体对牙髓组织的细胞毒性是影响保髓疗效的不利因素。我们前期研究发现抗菌粘接剂中的齿科单体是强亲电物质，且可通过过氧化损伤影响细胞的正常增殖及功能。Nrf2通路是细胞抵御过氧化损伤及亲电物质毒性"防御系统"中的关键环节，上调Nrf2通路可能有效缓解齿科单体的细胞毒性。课题组拟在前期工作基础上，研究齿科单体对Nrf2通路的影响及干预Nrf2表达后齿科单体细胞毒性的变化，探索多酚类物质原花青素能否通过上调Nrf2通路以缓解齿科单体及抗菌粘接剂的细胞毒性，进而改善抗菌粘接剂用于深龋保髓治疗的效果。本课题旨在阐明Nrf2通路对齿科单体及抗菌粘接剂细胞毒性的拮抗作用，为改善抗菌粘接剂保髓疗效提供新的理论及实验依据。

保存活髓是口腔医生追求的共同目标，但深龋患牙的活髓保存成功率低，是临床亟待解决的问题之一。含季铵盐单体的抗菌粘接剂具有良好的封闭及抗菌性能，为深龋的保髓治疗提供了新的选择，但其所含的各类单体对牙髓组织的细胞毒性是影响保髓疗效的不利因素。我们前期研究发现抗菌粘接剂中的齿科单体是强亲电物质，且可通过过氧化损伤影响细胞的正常增殖及功能。Nrf2通路是细胞抵御过氧化损伤及亲电物质毒性 “防御系统”中的关键环节，上调Nrf2通路可能有效缓解齿科单体的细胞毒性。在前期工作基础上，本课题研究了齿科单体引起细胞毒性的机理，并对Nrf2通路在单体引起毒性过程中的变化及人为干预Nrf2表达后齿科单体细胞毒性的变化进行探索，初步探讨了多酚类物质原花青素能否通过上调Nrf2以缓解齿科单体及抗菌粘接剂的细胞毒性作用，进而改善抗菌粘接剂用于深龋保髓治疗的效果。研究结果表明齿科单体通过过氧化损伤引起人牙髓细胞发生DNA损伤、细胞周期阻滞及内源性凋亡的发生。在齿科单体引起细胞毒性的过程中，Nrf2通路被激活，多种保护性抗氧化酶的表达及活性发生变化。人为上调Nrf2通路可进一步提高保护性酶的表达，进而降低齿科单体的毒性作用，而人为下调Nrf2通路则有相反作用。原花青素可上调Nrf2通路，缓解齿科单体及抗菌粘接剂的毒性作用，进而改善抗菌粘接剂用于直接盖髓的效果。本课题阐明了齿科单体引起细胞毒性的作用，以及Nrf2通路对齿科单体及抗菌粘接剂细胞毒性的拮抗作用，为改善抗菌粘接剂保髓疗效提供新的理论及实验依据。