踝蛋白-1调控小鼠主动脉夹层血管重构的机制研究  

Mechanism of Talibin-1 regulating vascular remodeling of aortic dissection in mice

作　　者：孙羽东 王诗颖 朱江 韩同磊 闻荻豪 杨静[3] 景在平 周建 赵志青 魏小龙 Sun Yudong;Wang Shiying;Zhu Jiang;Han Tonglei;Wen Dihao;Yang Jing;Jing Zaiping;Zhou Jian;Zhao Zhiqing;Wei Xiaolong(Depaertment of Ceneral Surgery,Jinling Hospital,Nanjing University,Nanjing 210002,China;Departmentof Vascular Surgery,Changhai Hospital,Naval Medical University,Shanghai 200433,China;Department ofGeneral Surgery,Shanghai Seventh People's Hospital,Shanghai 200137,China)

机构地区：[1]南京大学医学院附属金陵医院(解放军东部战区总医院)普通外科,210002 [2]海军军医大学第一附属医院血管外科,上海200433 [3]上海市第七人民医院普通外科,200137

出　　处：《中华普通外科杂志》2021年第1期25-29,共5页Chinese Journal of General Surgery

基　　金：上海市卫生和计划生育委员会科研课题(20184Y0313);国家自然科学基金(82000464,81770482);浦东新区卫生系统特色专病建设资助项目(PWZ262017-13)。

摘　　要：目的探索踝蛋白-1(Talin-1)在小鼠主动脉夹层中的作用与机制。方法FVB雄性小鼠共60只,分为空白组,造模组,Talin-1上调组,Talin-1上调对照组,Talin-1下调组,Talin-1下调对照组,每组10只。除空白组外,其余组均给予β-氨基丙腈结合血管紧张素构建小鼠主动脉夹层模型。利用腺相关病毒技术进行小鼠体内干预'Talin-1。用苏木精-伊红和血管弹力纤维染色(EVC)观察主动脉和弹力纤维的形态和结构。用Western blot法检测小鼠主动脉组织中FAK和ERK1/2的磷酸化水平。结果﹑造模组小鼠主动脉夹层造模成功率70%,空白组未出现主动脉夹层。所有小鼠在实验期间未出现猝死。Talin-1下调组小鼠主动脉夹层发生率100%,显著高于Talin-1下调对照组,Talin-1上调组小鼠主动脉夹层发生率20%,显著低于Talin-1上调对照组(均P<0.05)。苏木精-伊红染色和EVC结果提示Talin-1下调组小鼠主动脉管壁增厚,伴壁间血肿或假腔形成,同时中膜弹力纤维含量与Talin-1下调对照组相比显著降低,而Talin-1上调组小鼠血管壁中弹力纤维含量显著高于Talin-1上调对照组(均P<0.05)。Western blot检测发现下调Talin-1显著抑制FAK磷酸化,相反对ERK1/2磷酸化起到促进作用(均P<0.05)。结论Talin-1下调可能通过激活ERK1/2信号通路进而降低小鼠主动脉中膜弹力纤维含量,导致主动脉管壁发生血管重构,促进主动脉夹层的发生。Objective To explore the role and mechanism of Talin-1 in mouse aortic dissection.Methods Sixty male FVB mice were evenly divided into groups of blank,model,Talin-l up-regulation,Talin-1 up-regulation control,Talin-1 doyn-regulation,and Talin-1 down-regulation control.Except mice inthe blank group,mice were treated with B-aminopropionitrile(BAPN)combined with angiotensin toconstruct a mouse aortic dissection model.Hematoxylin-cosin and vascular elastic fiber staining(EVG)wereused to observe the aorta and elastic fiber morphology and structure.Westernm blot was used to detect thephosphorylation levels of FAK and ERK1/2 in mouse aortic tissue.Results The success rate of aorticdissection in model mice was 70%,and there was no aortic dissection appeared in the blank group.No micedied during the experiment.The incidence of aortic dissection in the Talin-1 down-regulated group was100%,which was significantly higher than that in the'Talin-1 down-regulated control group(P<0.05).Theincidence of aortic dissection in the Talin-1 up-regulated group was 20%,significantly lower than that in theTalin-l up-regulated control group.The wall thickness of the aorta of mice in the Talin-1 down-regulatedgroup was accompanied by hematoma or pseudocavity formation.The median elastic fiber content was higher than that in the'Talin-l downregulation control group(P<0.05).The content of elastic fibers in the bloodvessel wall of mice in the Talin-1 up-regulation group was significantly higher than that in the Talin-l up-regulation control group.The down-regulation of Talin-l significantly inhibited FAK phosphorylation,andinstead promoted ERK1/2 phosphorylation(P<0.05).Conclusions Down-regulation of Talin-1 mayreduce the elastic fiber content in the aorta of mice by activating the ERK1/2 signaling pathway,leading tovascular remodeling of the aortic wall and promoting the occurrence of aortic dissection.

关 键 词：主动脉疾病 踝蛋白 血管重构 ERK1/2 

分 类 号：R543.1[医药卫生—心血管疾病]