低值海参促进小鼠骨折愈合及机制研究  

Acaudina molpadioidea Promotes Fracture Healing and Its Mechanism

作　　者：李卓 田迎樱 李媛媛 闫子怡 傅安妮 王静凤[1] Li Zhuo;Tian Yingying;Li Yuanyuan;Yan Ziyi;Fu Anni;Wang Jingfeng(College of Food Science and Engineering,Ocean University of China,Qingdao 266003,Shandong;Marine Biomedical Research Institute of Qingdao,Qingdao 266000,Shandong)

机构地区：[1]中国海洋大学食品科学与工程学院,山东青岛266003 [2]青岛海洋生物医药研究院,山东青岛266000

出　　处：《中国食品学报》2022年第1期88-97,共10页Journal of Chinese Institute Of Food Science and Technology

基　　金：“十三五”国家重点研发计划重点专项(2018YFC0311203)。

摘　　要：海地瓜是产自东南沿海的一种低值海参,具有降血糖,降血脂,抗氧化等活性,而其对骨折愈合的研究尚未见报道。对8周龄雌性C57BL/6小鼠进行右侧胫骨开放性骨折手术构建骨折模型,在模型小鼠灌胃海地瓜(500 mg/kg BW)后的第5,10,21天取材,检测各组血清指标、组织形态学、软骨内成骨关键基因的转录水平,探究海地瓜对骨折愈合过程的影响及机制。结果表明,术后第10天,海地瓜组血清Aggrecan、Col10α浓度较模型组显著降低了12.1%和19.31%,MMP13浓度显著提高了14.91%,提示与模型组相比,海地瓜组软骨细胞提前由增殖转变为肥大分化状态,加快了愈合进程。H&E染色结果表明,与模型组相比,海地瓜干预能促进术后第5天纤维骨痂的形成,术后第10天软骨性骨痂的形成及第21天板层骨的形成与硬骨痂的改建,提示海地瓜干预可加快软骨内骨化进程。q-PCR结果表明,术后第10天,海地瓜干预可激活Ihh和Smads/Runx2信号,下调通路关键因子Ihh、Patched、Gli1、Gli2及Smad1、Smad4、Smad5的转录水平,进而Col10α的转录显著下调,提示海地瓜干预使模型小鼠更快地渡过了软骨细胞的肥大阶段,进入矿化成骨时期,此时骨生成因子ALP、Col1α转录水平的显著升高也进一步证明海地瓜加速骨折愈合的能力。结论:海地瓜可通过介导Ihh及Smads/Runx2信号通路调控软骨肥大,加速软骨内骨化进程,以促进骨折愈合,其效果与仿刺参相当。本研究为海地瓜的深度开发及在骨折愈合方面的应用提供了理论依据。Acaudina molpadioides is a low-value sea cucumber produced from the southeast coast.It is inexpensive and has hypoglycemic,hypolipidemic,and antioxidant activities.However,its effect on fracture healing has not been reported.In this study,Female C57 BL/6 mice underwent right tibia open fracture surgery and were randomly divided into model control group,Apostichopus japonicus group(500 mg/kg BW) and Acaudina molpadioides group(500 mg/kg BW).The tests were performed on the 5 th,10 th,and 21 stdays to explore the effect and mechanism of Acaudina molpadioides on the fracture healing process.Serum dynamic test results showed that on the 10 thpostoperative day,the serum Col10α concentration in the Acaudina molpadioides group was significantly reduced by 19.31% compared with the model group,and the serum MMP13 by 14.91%.It is suggested that compared with the model group,the chondrocytes in the Acaudina molpadioides group changed from proliferation to hypertrophy and differentiation in advance,which accelerated the healing process.H&E staining results show that compared with the model group,the intervention of Acaudina molpadioides and Apostichopus japonicus can promote the formation of fibrous callus on the 5 thpostoperative day,postoperative The formation of cartilage callus on day 10 and the formation of lamellar bone and the reconstruction of hard callus on day 21 suggest that the intervention of Acaudina molpadioides can accelerate the process of ossification in cartilage.Further q-PCR results showed that on the 10 th day after surgery.The intervention of Acaudina molpadioides can activate Ihh and Smads/Runx2 signals,and down-regulate the transcription levels of key factors Ihh,Patched,Gli1,Gli2 and Smad1,Smad4,Smad5,and the transcription of Col10α is significantly down-regulated,suggesting that Acaudina molpadioides intervention can cross the cartilage faster.The hypertrophic stage of the cells enters the period of mineralization and osteogenesis.At this time,the significant increase in the transcription level of

关 键 词：海地瓜 仿刺参 骨折愈合 软骨内骨化 IHH Smads/Runx2 

分 类 号：TS254.1[轻工技术与工程—水产品加工及贮藏工程]