首页|期刊导航|口腔疾病防治|微波辐射加重实验性牙周炎小鼠认知功能损伤的研究

微波辐射加重实验性牙周炎小鼠认知功能损伤的研究OA

Study on microwave radiation aggravating the impairment of cognitive functions in mice with experimental periodontitis

中文摘要英文摘要

目的 探讨微波辐射对实验性牙周炎小鼠认知功能及神经炎症的影响,为理解环境暴露如何通过调控慢性炎症这一共同病理机制,进而与神经退行性疾病风险相关联提供实验依据.方法 本研究获得军事医学研究院动物伦理委员会批准.将C57BL/6J小鼠随机分为对照组(C组,未做处理)、微波辐射组(R组,仅微波辐射暴露)、牙周炎组(P组,仅结扎造模)和牙周炎+微波辐射组(PR组,结扎造模及微波辐射暴露).采用丝线结扎法建立牙周炎模型,并于造模8周后对R组与PR组进行2 800 MHz、10 mW/cm2的微波全身辐射,10 h/d,持续7 d.进行行为学测试:采用旷场实验和高架十字迷宫实验评估小鼠的焦虑样情绪,通过Y迷宫实验评估小鼠的空间记忆能力,并利用新物体识别实验评估小鼠的学习记忆能力.采用Micro-CT、苏木精-伊红染色法(HE)和实时荧光定量(qPCR)分析牙周组织病理与局部炎症;通过酶联免疫吸附实验(ELISA)检测血清及脑组织中脂多糖(LPS)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平;基于16S rRNA测序分析口腔菌群组成.结果 行为学测试表明,R组与PR组小鼠焦虑样行为显著加剧,且PR组与P组的空间与识别记忆损伤分别较R组与C组加重(P<0.05).组织与分子生物学分析显示,PR组与P组牙周炎症浸润、牙槽骨吸收及局部促炎因子 TNF-α、IL-1β、IL-6表达均分别较 R组与 C组进一步加剧(P<0.05).ELISA结果显示,血清中,P组与PR组LPS水平分别较C组与R组升高,PR组TNF-α、IL-1β、IL-6水平显著高于P组及R组,且TNF-α水平协同性升高(P<0.05);脑组织中,P组LPS及TNF-α、IL-1β、IL-6水平显著高于C组,PR组上述指标显著高于P组及R组,且LPS与IL-6水平协同性升高(P<0.05).口腔菌群分析发现,微波辐射在牙周炎基础上进一步降低了菌群多样性,并导致乳杆菌属、肠球菌属等菌群相对丰度增加,而葡萄球菌属等菌群相对丰度减少.相关性分析证实,这些差异菌属与脑组织炎症水平正相关,与认知功能指标负相关.结论 微波辐射暴露可加剧实验性牙周炎小鼠的认知功能损伤,其机制可能与加重牙周局部破坏、扰乱口腔菌群稳态进而诱导全身及中枢神经炎症的级联反应有关.

Objective To explore the effects of microwave radiation on cognitive function and neuroinflammation in mice with experimental periodontitis,providing experimental evidence for understanding how environmental exposure may be linked to the risk of neurodegenerative diseases by modulating chronic inflammation as a shared pathological mechanism.Methods This study was approved by the Animal Ethics Committee of the Academy of Military Medical Sciences.C57BL/6J mice were randomly divided into a control group(C group,untreated),a microwave radiation group(R group,exposed to microwave radiation only),a periodontitis group(P group,ligation-induced periodontitis only),and a periodontitis+microwave radiation group(PR group,ligation-induced periodontitis plus microwave radiation expo-sure).A periodontitis model was established using the silk ligation method.Eight weeks after modeling,the R and PR groups were subjected to whole-body microwave radiation at 2 800 MHz and 10 mW/cm2 for 10 h/day for 7 consecutive days.Behavioral tests were conducted:the open field test and elevated plus maze test were used to assess anxiety-like behavior,the Y-maze test to evaluate spatial memory,and the novel object recognition test to assess learning and memory abilities.Micro-CT,hematoxylin&eosin staining(HE),and quantitative real-time polymerase chain reaction(qPCR)were used to analyze periodontal tissue pathology and local inflammation.Serum and brain levels of lipopolysac-charide(LPS),interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)were measured using enzyme-linked immunosorbent assay(ELISA).The composition of the oral microbiota was analyzed based on 16S rRNA sequencing.Results Behavioral tests showed that anxiety-like behavior was significantly exacerbated in the R and PR groups,and spatial and recognition memory impairments in the PR and P groups were more severe compared with the R and C groups,respectively(P<0.05).Histological and molecular biological analyses revealed that periodontal inflam-mation infiltration,alveolar bone resorption,and local expression of pro-inflammatory cytokines(TNF-α,IL-1β,IL-6)were further exacerbated in the PR and P groups compared with the R and C groups,respectively(P<0.05).ELISA re-sults showed that in serum,LPS levels in group P and group PR were increased compared with group C and group R,re-spectively.The levels of TNF-α,IL-1β,and IL-6 in group PR were significantly higher than those in group P and group R,with a synergistic increase in TNF-α level(P<0.05).In brain tissue,LPS and TNF-α,IL-1β,IL-6 levels in group P were significantly higher than those in group C;all the above indicators in group PR were significantly higher than those in group P and group R,and LPS and IL-6 levels showed a synergistic increase(P<0.05).Oral microbiota analy-sis found that microwave radiation further reduced microbial diversity on the basis of periodontitis,leading to increased relative abundances of Lactobacillus and Enterococcus,and decreased relative abundances of Staphylococcus.Correlation analysis confirmed that these differential bacterial genera were positively correlated with brain inflammation levels and negatively correlated with cognitive function indicators.Conclusion Microwave radiation exposure can exacerbate cog-nitive impairment in mice with experimental periodontitis,and its mechanism may be related to aggravated local peri-odontal damage,disruption of oral microbiota homeostasis,and subsequent induction of systemic and central neuroin-flammatory cascades.

周虹瑾;王健辉;刘琳;李鸿波

中国人民解放军总医院第一医学中心口腔科,北京(100853)||中国人民解放军医学院,北京(100853)军事医学研究院,北京(100850)中国人民解放军总医院第一医学中心口腔科,北京(100853)中国人民解放军总医院第一医学中心口腔科,北京(100853)

医药卫生

微波辐射牙周炎认知功能口腔菌群神经炎症协同作用16S rRNA系统性炎症

microwave radiationperiodontitiscognitive functionoral microbiotaneuroinflammationsynergistic effect16S rRNAsystemic inflammation

《口腔疾病防治》 2026 (6)

541-555,15

10.12016/j.issn.2096-1456.202660020

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