昼夜节律紊乱对骨折愈合进程的抑制效应研究  

Study on inhibitory effect of circadian rhythm disorders on fracture healing process

作　　者：齐凤 刘洋[1] 钟研 郑凝浩 薛徽 Qi Feng;Liu Yang;Zhong Yan;Zheng Ninghao;Xue Hui(Qiqihar Medical University,Qiqihar,Heilongjiang 161006,China)

机构地区：[1]齐齐哈尔医学院,黑龙江齐齐哈尔161006

出　　处：《齐齐哈尔医学院学报》2025年第4期301-307,共7页Journal of Qiqihar Medical University

基　　金：齐齐哈尔医学院研究生创新基金项目(QYYCX2022-38);齐齐哈尔市科技计划联合引导项目(LSFGG-2023051)。

摘　　要：目的 探究昼夜节律紊乱(Circadian rhythm disorder, CRD)对小鼠股骨骨折愈合的影响并初步探索其可能的相关机制。方法 6~8周龄体质量为(20+2)g雄性C57 BL/6J小鼠40只,2周适应性饲养后按随机数字表达法分为正常昼夜节律(Normal circadian rhythm, NCR)组和昼夜节律紊乱(Circadian rhythm disorder, CRD)组。在8周的节律紊乱干预后,再分别构建NCR组及CRD组股骨骨折模型。模型构建完毕后,于7 d、14 d、21 d及28 d分别采集股骨样本。随后,利用高分辨率显微计算机断层扫描技术(micro-CT)对骨折区域进行精细扫描,并定量评估其骨体积分数(Bone volume/Total volume, BV/TV),通过组织样本的切片处理与特定的染色技术,观察两者间骨折断端处组织修复与愈合状况的差异;通过免疫荧光染色,探究骨折发生后2周内,组织受损区域内成骨及成软骨相关蛋白的表达水平变动差异。结果 HE和TB染色结果显示,NCR组的愈合进程快于CRD组。Micro-CT量化结果显示,股骨骨折术后7 d、14 d、21 d及28 d后CRD组的BV/TV明显低于NCR组(P<0.0001)。免疫荧光化学染色结果显示骨折后14 d NCR组的成骨和成软骨相关蛋白表达量明显高于CRD组。结论 昼夜节律紊乱会显著抑制骨形成及骨折愈合进程。Objective To investigate the impact of circadian rhythm disorder(CRD)on femur fracture healing in mice and to preliminarily explore its possible related mechanisms.Methods Forty male C57BL/6J mice,aged 6–8 weeks and weighing(20±2)g,were selected for the study.After a 2-week acclimation period,the mice were randomly divided into two groups using a random number table:the Normal Circadian Rhythm group(NCR)and the Circadian Rhythm Disorder group(CRD).Following an 8-week circadian rhythm disturbance intervention,femoral fracture models were established for both the NCR and CRD groups.Post-model construction,femoral samples were collected at 7,14,21,and 28 days.High-resolution micro-computed tomography(micro-CT)was employed to precisely scan the fracture sites and quantitatively assess bone volume fraction(bone volume/total volume,BV/TV).Histological sectioning and specific staining techniques were used to observe differences in tissue repair and fracture healing at the fracture ends between the two groups.Additionally,immunofluorescence staining was applied to investigate differences in the expression levels of osteogenesis-and chondrogenesis-related proteins within the injured regions during the first 2 weeks post-fracture.Results HE and TB staining showed that the healing process of the NCR group was faster than that of the CRD group,and micro-CT quantification showed that the BV/TV of the CRD group was significantly lower than that of the NCR group at 7,14,21,and 28 d after femur fracture surgery(P<0.0001).Immunofluorescence staining showed that the expression of osteogenic and chondrogenic proteins in the NCR group was significantly higher than that in the CRD group 14 d after fracture.Conclusions Circadian rhythm disruption significantly inhibits the process of bone formation and fracture healing.

关 键 词：昼夜节律现象 骨折愈合 骨重建 骨修复 

分 类 号：R683[医药卫生—骨科学]