Yan Jiaqing, Liu Min, Zhang Yan, Zhu Ying, Chen Qiuyan, Yang Yimeng, Hu Min, Yu Huimei
Hospital of Stomatology, Jilin University, Changchun 130021, China.
Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
Biomimetics (Basel). 2022 Dec 14;7(4):240. doi: 10.3390/biomimetics7040240.
Periodontitis is an inflammatory disease induced by plaque microorganisms. In the clinic, antibiotic assistant periodontal mechanical therapy is the most effective therapy for the treatment of periodontitis. However, the drug resistance of the antibiotics and the repeated coming and diminishing of the disorder of oxidation-reduction balance in the inflammatory tissue could not meet the high requirements for periodontic health control in long periods. Deuterohemin-ala-his-thr-val-glu-lys (DhHP-6) is a biomimetic oxidase-mimicking enzyme that simulates the reactive oxygen radical scavenger function of heme by synthesizing the new molecular material following the key structure and amino acid sequence of heme. In this article, we report the antioxidant and anti-inflammatory properties of DhHP-6 by building a inflammatory model for human gingival fibroblasts (HGFs) stimulated by lipolysaccharide (LPS) and its effects on periodontitis in Wistar rats. DhHP-6 reduced the oxidative stress of HGFs by increasing the amount of the reductase species of glutathione (GSH) and catalase (CAT) while decreasing the amount of oxidase species of malonaldehyde (MDA) and reactive oxygen species (ROS). DhHP-6 had a dose-dependent protective effect on alveolar bone absorption in rats with periodontitis, enhanced antioxidant capacity, and reduced inflammation. As determined by Micro-CT scanning, DhHP-6 reduced alveolar bone loss and improved the bone structure of the left maxillary first molar of rats. There were no obvious morphological and histological differences in the rat organs with or without DhHP-6 treatment. These results suggest that DhHP-6 can be used to treat periodontitis by increasing the expression levels of antioxidant enzymes and antioxidants in systemic and local tissues, thereby reducing levels of oxidation products and cyto-inflammatory factors. The synergistic antioxidant and anti-inflammatory effects of DhHP-6 suggest that there are promising applications of this biomimetic enzyme molecular material for the next generation of agents for periodontitis therapy.
牙周炎是一种由菌斑微生物引起的炎症性疾病。在临床上,抗生素辅助牙周机械治疗是治疗牙周炎最有效的方法。然而,抗生素的耐药性以及炎症组织中氧化还原平衡紊乱的反复出现和减轻,无法满足长期牙周健康控制的高要求。去铁血红素 - 丙氨酸 - 组氨酸 - 苏氨酸 - 缬氨酸 - 谷氨酸 - 赖氨酸(DhHP - 6)是一种仿生氧化酶模拟酶,它通过按照血红素的关键结构和氨基酸序列合成新的分子材料来模拟血红素的活性氧自由基清除功能。在本文中,我们通过构建脂多糖(LPS)刺激的人牙龈成纤维细胞(HGFs)炎症模型,报告了DhHP - 6的抗氧化和抗炎特性及其对Wistar大鼠牙周炎的影响。DhHP - 6通过增加还原型谷胱甘肽(GSH)和过氧化氢酶(CAT)等还原酶的量,同时减少丙二醛(MDA)和活性氧(ROS)等氧化酶的量,降低了HGFs的氧化应激。DhHP - 6对牙周炎大鼠的牙槽骨吸收具有剂量依赖性保护作用,增强了抗氧化能力并减轻了炎症。通过Micro - CT扫描确定,DhHP - 6减少了牙槽骨丢失,改善了大鼠左上颌第一磨牙的骨结构。DhHP - 6处理组和未处理组大鼠器官在形态和组织学上没有明显差异。这些结果表明,DhHP - 6可通过增加全身和局部组织中抗氧化酶和抗氧化剂的表达水平来治疗牙周炎,从而降低氧化产物和细胞炎症因子的水平。DhHP - 6的协同抗氧化和抗炎作用表明,这种仿生酶分子材料在下一代牙周炎治疗药物中具有广阔的应用前景。