Antioxidant effect of enamel matrix derivative for early phase of periodontal tissue regeneration in diabetes
Antioxidant effect of enamel matrix derivative for early phase of periodontal tissue regeneration in diabetes
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牙釉质基质衍生物对糖尿病牙周组织再生早期的抗氧化作用
DOI：
10.1002/jper.21-0413
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发表时间：
2022
影响因子：
4.3
通讯作者：
Iwata Takanori
中科院分区：
文献类型：
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作者：
Takeda Kohei;Mizutani Koji;Matsuura Takanori;Kido Daisuke;Mikami Risako;Buranasin Prima;Saito Natsumi;Kominato Hiromi;Takemura Shu;Nakagawa Keita;Iwata Takanori
背景糖尿病通过高血糖诱导的氧化应激引起多种组织的代谢紊乱。本研究旨在探讨釉基质衍生物（elaminmatrixderivatives，EMD）对糖尿病大鼠牙周组织再生的抗氧化作用。诱导高血糖后2个月，使用尿8-羟基-2 ′-脱氧鸟苷测量全身氧化应激。将EMD或生理盐水应用于双侧上颌磨牙的骨内缺损。定量炎症和氧化应激标志物的mRNA表达（n = 6）。术后7天（n = 5）进行组织学分析和超氧化物歧化酶-1（SOD-1）免疫组织化学。对于体外实验，从大鼠股骨中分离骨髓源性间充质干细胞，并在高葡萄糖（HG）或对照培养基中培养。活性氧（ROS）的测量和茜素红染色进行与/无EMD。ResultsSystemic oxidative stress显着高于糖尿病组。在糖尿病和非糖尿病组中，EMD治疗部位的结缔组织附着和牙骨质形成显著增加。在糖尿病和非糖尿病大鼠中，EMD处理部位的烟酰胺腺嘌呤二核苷酸磷酸氧化酶2和4的表达显著低于EMD未处理部位。免疫组织化学显示EMD处理部位的SOD-1表达显著升高。在体外，HG培养物的活性氧产生量显着高于对照组，而对照组的活性氧产生量被EMD下调。EMD治疗显着恢复受损的钙化在HG。结论EMD促进早期阶段的伤口愈合和牙周组织再生的骨缺损的STZ诱导的糖尿病大鼠通过抑制高血糖诱导的氧化应激。
BackgroundDiabetes involves metabolic disorders in various tissues via hyperglycemia‐induced oxidative stress. This study aimed to investigate the antioxidative effect of enamel matrix derivative (EMD) on periodontal regeneration in diabetes.MethodsTwenty‐two rats were equally divided into streptozotocin (STZ)‐induced diabetes or control group. Two months after induction of hyperglycemia, systemic oxidative stress was measured using urinary 8‐hydroxy‐2′‐deoxyguanosine. EMD or saline was applied into the intrabony defects created in the bilateral maxillary molar. mRNA expressions of inflammatory and oxidative stress markers were quantified (n = 6). Histometric analyses and immunohistochemistry of superoxide dismutase‐1 (SOD‐1) were performed 7 days postoperatively (n = 5). For in vitro experiments, the bone marrow‐derived mesenchymal stem cells were isolated from rat femur and cultured in a high glucose (HG) or control medium. Reactive oxygen species (ROS) measurement and alizarin red staining were performed with/without EMD.ResultsSystemic oxidative stress was significantly higher in the diabetic group. The connective tissue attachment and cementum formation were significantly increased at EMD‐treated sites in both diabetic and non‐diabetic groups. The expression of nicotinamide adenine dinucleotide phosphate oxidase two and four was significantly lower at EMD‐treated sites than at EMD‐untreated sites in both diabetic and non‐diabetic rats. Immunohistochemistry showed significantly higher SOD‐1 expression at the EMD‐treated site. In vitro, HG culture had significantly higher ROS production compared with control, which was downregulated by EMD. EMD treatment significantly recovered the impaired calcification in HG.ConclusionEMD promoted early‐phase wound healing and periodontal tissue regeneration in the surgically created bony defect of STZ‐induced diabetic rat by suppressing hyperglycemia‐induced oxidative stress.