FAK/Twist1信号通路在颅缝闭合过程中的作用机制研究  

The mechanism of FAK/Twist1 signal pathway in the closure of cranial suture

作　　者：寇正雄 张海燕[4] 邵国[2,3] 张晓璐 张春阳 侯晓峰[1,2,3] Kou Zhengxiong;Zhang Haiyan;Shao Guo;Zhang Xiaolu;Zhang Chunyang;Hou Xiaofeng(Dept of Neurosurgery,The First Affiliated Hospital of Baotou Medical College,Baotou 014000;Institute of Neurosurgical Diseases,Baotou Medical College(Translational Medicine),Baotou 014000;Inner Mongolia Autonomous Region Bone Tissue Regeneration and Injury Repair Engineering Technology Center,Baotou 014000;The Third Ward of Neurology,The First Affiliated Hospital of Baotou Medical College,Baotou 014000)

机构地区：[1]内蒙古科技大学包头医学院第一附属医院神经外科,包头014000 [2]包头医学院神经外科疾病研究所(转化医学),包头014000 [3]内蒙古自治区骨组织再生与损伤修复工程技术中心,包头014000 [4]内蒙古科技大学包头医学院第一附属医院神经内三科,包头014000

出　　处：《安徽医科大学学报》2023年第1期60-66,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82160250,81960238);内蒙古自治区自然科学基金(编号:2020MS08013,2021MS08124);内蒙古卫生厅(编号:202202234);包头医学院科学研究基金(编号:BYJJ-QM 201928)。

摘　　要：目的探究FAK/Twist1信号通路在颅缝闭合过程中的作用。方法将10 d大鼠分为对照组(50只)和颅缝旋转组(50只),以大鼠人字缝中点为中心,直径约0.5 cm做一骨窗,将骨瓣在不损伤硬脑膜的情况下游离,对照组骨瓣原位复位,旋转组骨瓣旋转180°后复位,两组大鼠3周后进行实验。旷场试验测试行为学,测量两组体质量、头围、骨瓣面积、骨瓣厚度等生理学指标,显微镜及HE染色观察颅缝闭合情况,Western blot、Real time PCR、免疫组化染色测定骨瓣及骨瓣下硬脑膜FAK/Twist1通过表达情况。结果旋转组骨瓣厚度大于对照组,差异有统计学意义(P<0.01),头围、体质量、骨瓣面积、术区面积无明显差异;显微镜下及HE染色中结果显示:旋转组颅缝完全闭合,对照组颅缝保持正常形态;行为学试验结果显示,颅缝闭合后大鼠行动能力下降且出现抑郁倾向;Western blot、Real time PCR、免疫组化染色显示:旋转组FAK在颅骨和硬脑膜中表达量均高于对照组且差异有统计学意义(P<0.05),旋转组Twist1在硬脑膜中表达量低于对照组且差异有统计学意义(P<0.05),在颅骨中两组Twist1表达量相近,差异无统计学意义。结论颅缝旋转后可以导致颅缝早闭,并会出现行动能力下降等行为学异常,FAK/Twist1可能在颅缝闭合过程中发挥着重要作用。Objective To investigate the function of FAK/Twist1 signaling pathway during craniosynostosis closure.Methods Ten days old rats were divided into a control group(n=50)and a rotation group(n=50).Both of them were made a approximately 0.5 cm circle bone window at the midpoint of the lambdoid suture of the rat.The bone flaps were left free without damaging the dura mater.The bone flaps in the control group were repositioned in situ,and the bone flaps in the rotation group were rotated 180°and repositioned 3 weeks later.Then the experiments were performance as followed:open field test,measurement of body weight,head circumference,bone flap area,and thickness of bone flap in the two groups,observation of cranial suture closure by microscopy and HE staining,FAK/Twist1 expression determined by Western blot,real-time PCR,and immunohistochemical staining in the bone flap and dure,respectively.Results The cranial sutures was completely closed in the rotation groupand that was open in the control group through detecting by microscopic examination and HE staining.The thickness of the bone flap in the derotation group was greater than that in the control group,with statistical significance(P<0.01).There were no significant differences between two groups in head circumference,weight,bone flap area,and operative area.The results of behavioral test showed that after the closure of cranial suture,the action ability of rats decreased and showed a tendency of depression.Compared with that in control group,the expression of FAK was significantly increased in the calvaria and dura as well as Twsit1 was significantly decreased in the dura in rotating group measuring by Western blot,real-time PCR,and immunohistochemical staining(P<0.05).Conclusion FAK/Twist1 may play an important role in craniosynostosis after rotation.

关 键 词：黏着斑激酶 TWIST1 颅缝闭合 狭颅症 信号通路 颅缝旋转 

分 类 号：R651.11[医药卫生—外科学]