基于MOF的2D“纳米盔甲”保护能量代谢核心-电子传递链抑制过度免疫应答在治疗糖尿病种植体周围炎中的作用机制研究

糖尿病患者种植体周围炎发病风险较正常人群更高，与高糖影响能量代谢、干扰局部免疫-炎症应答有关。ROS是能量代谢障碍调控免疫细胞分化的关键效应因子，可通过攻击线粒体电子传递链推动过度免疫应答。课题组前期发现高糖炎性环境下免疫细胞代谢方式转变、促炎型分化增加；可变价态铈离子可通过氧化还原特性模拟SOD/CAT清除ROS，保护线粒体电子传递链。推论：糖尿病患者处于能量代谢失衡的慢性炎症状态，二者交互放大使ROS堆积，超量ROS严重损害电子传递链，促进巨噬细胞及T细胞促炎型分化，局部炎症风暴降临。基于该理论，项目组拟以糖尿病环境下线粒体电子传递链受损为切入点，阐释其加重氧化应激、放大炎症效应的关键环节；继而，验证基于金属-有机骨架策略合成的2D“纳米盔甲”通过重构SOD/CAT动态平衡，保护电子传递链，降调局部氧化应激，重建种植体周生理稳态的作用及分子机制，自代谢-免疫角度为该病的防治提供新策略。

Diabetes patients suffer from a higher risk of peri-implantitis, which is significantly related to the metabolic disorders and local immune-inflammatory response caused by hyperglycemic interference. ROS may mediate the differentiation of immune cells affected by metabolic disorders and promote excessive immune responses through attacking mitochondrial complex. Our research team has previously proven that the immune cells of the peri-implantitis under diabetic condition tend to differentiate into pro-inflammatory type and the transformation of metabolism is detected simultaneously; the cerium ion under variable valence state can remove ROS and protect mitochondrial electron chain by simulating SOD/CAT due to its oxidation-reduction quality. Therefore, we speculate that chronic inflammatory state is generated through diabetes, where the accumulation of ROS occurred under the interactive amplification effect. The overwhelming ROS causes damage to the electron transfer chain and promotion of macrophages and T cells to differentiate into pro-inflammatory phenotype, which further amplifies inflammatory response. Based on the above hypothesis, our study will target at the damage of mitochondrial electron transport chain under diabetic condition, and further explain the critical factor that aggravates oxidative stress and amplifies the inflammatory effect. Moreover, we aim to confirm the protective potential of dynamic 2D nano-armor based on metal-organic framework, which can precisely simulate SOD / CAT rebalance, protect electron transfer chain, and down-regulate oxidative stress to restore peri-implant physiological homeostasis. Our study will provide a new strategy for the prevention and treatment of diabetic peri-implantitis from an immunometabolic perspective.