夜间光污染抑制褪黑素分泌影响发育期颌骨糖代谢的实验研究  

Artificial light at night effects glucose metabolism in the developing jawbone by inhibiting melatonin secretion

作　　者：唐清明 尹盈 陈莉莉 Tang Qingming;Yin Ying;Chen Lili(Department of Stomatology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology&School of Stomatology,Tongji Medical College,Huazhong University of Science and Technology&Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration,Wuhan 430022,China;Department of Orthodontics,Hospital of Stomatology,Guanghua School of Stomatology,Sun Yat-sen University&Guangdong Provincial Key Laboratory of Stomatology,Guangzhou 510055,China)

机构地区：[1]华中科技大学同济医学院附属协和医院口腔医学中心,华中科技大学同济医学院口腔医学院,口腔颌面发育与再生湖北省重点实验室,武汉430022 [2]中山大学附属口腔医院正畸科·中山大学光华口腔医学院·广东省口腔医学重点实验室,广州51005

出　　处：《中华口腔医学杂志》2025年第2期140-150,共11页Chinese Journal of Stomatology

基　　金：国家自然科学基金(U23A20443, 82270950, 82030070);华中科技大学“基础研究支持计划”(2023BR032)。

摘　　要：目的探究夜间光污染对小鼠下颌骨生长的影响及其调控机制。方法通过控制光照时间模式差异, 构建夜间光污染(夜间光污染组)和正常光照(正常光照组)的小鼠动物模型, 每组4只。采用显微CT分析两组小鼠下颌骨骨量差异, 使用实时荧光定量PCR(RT-qPCR)检测小鼠下颌骨骨皮质和髁突成骨中心的成骨分化、代谢相关基因的表达水平差异。通过酶联免疫吸附测定法检测两组小鼠血清褪黑素浓度的昼夜差异。夜间光污染补充褪黑素组小鼠通过每天定时定量注射褪黑素恢复血清褪黑素浓度的昼夜差异, 正常光照组和夜间光污染组注射相同体积的生理盐水, 分别检测3组小鼠下颌骨骨量、下颌骨组织形态、髁突成骨中心和骨皮质的成骨分化、糖代谢表达的差异。结果夜间光污染组小鼠下颌骨骨皮质厚度[(0.196±0.017)mm]、下颌骨髁突成骨中心骨体积分数[(36.90±1.09)%]及下颌骨长度[(10.86±0.17)mm]均显著小于正常光照组小鼠[分别为(0.228±0.007)mm、(54.24±1.49)%、(11.41±0.32)mm](P=0.029, P<0.001, P=0.032)。RT-qPCR结果显示, 夜间光污染组小鼠下颌骨骨皮质和髁突成骨中心的成骨相关基因肝/骨/肾型碱性磷酸酶(Alpl)、骨钙素(Ocn)、Runt相关转录因子2(Runx2)、成骨细胞特异性转录因子(Osx)基因的表达均显著低于正常光照组(均P<0.05)。夜间光污染组小鼠下颌骨骨皮质和髁突成骨中心代谢相关基因腺苷活化蛋白激酶α1亚基(Prkaa1)、ATP酶H+转运V0亚基D1(Atp6v0d1)、细胞色素C氧化酶亚基Ⅳ亚型1[Cox4il(基因)/COX Ⅳ(蛋白)]表达相比正常光照组小鼠均显著减少(均P<0.01)。正常光照组小鼠血清褪黑素浓度高峰出现在关灯8 h后, 而夜间光污染组小鼠夜间血清褪黑素浓度与正常光照组相比显著降低且无明显峰值(P<0.05)。显微CT结果显示, 夜间光污染补充褪黑素组小鼠下颌骨骨皮质厚度、髁突成骨中心骨体积分�ObjectiveTo investigate the effects of artificial light at night on the growth of mandibles in mice and its regulatory mechanisms.MethodsA mouse model of artificial light at night(night light pollution group)and normal lighting(normal light group)was established by controlling light exposure time,with 4 mice in each group.Micro-CT was employed to analyze the differences in bone quantities of the mandibles between the two groups.Real-time fluorescence quantitative PCR(RT-qPCR)was used to examine the expression levels of osteogenic differentiation and metabolism-related genes in the cortical bone and condylar ossification center of the mandibles.Enzyme-linked immunosorbent assay was utilized to assess the diurnal variation of serum melatonin concentrations between the two groups.The artificial light at night experimental group received daily timed injections of a defined dose of melatonin to restore the diurnal variation of serum melatonin concentration in the mice,while the normal light group and the artificial light at night control group received the same volume of saline.Bone quantities,mandibular tissue morphologies,ossification differentiation in the condylar region and cortical bone,as well as glucose metabolism expression differences were assessed across the three groups.ResultsThe cortical bone thickness of the mandibles in the artificial light at night group[(0.196±0.017)mm]was significantly less than that in the control group[(0.228±0.007)mm](P=0.029).The bone volume fraction of the condylar ossification center in the artificial light at night group[(36.90±1.09)%]was significantly lower than that in the normal light group[(54.24±1.49)%](P<0.001).The length of the mandible in the artificial light at night group[(10.86±0.17)mm]was significantly shorter than that in the normal light group[(11.41±0.32)mm](P=0.032).RT-qPCR results indicated that the expressions of osteogenic-related genes alkaline phosphatase,liver/bone/kidney(Alpl),osteocalcin(Ocn),Runt-related transcription factor 2(Runx2),and osterix

关 键 词：骨发育 糖代谢 下颌骨 成骨活动 夜间光污染 褪黑素 

分 类 号：R782[医药卫生—口腔医学]