上调Yes相关蛋白1表达抑制动脉夹层血管平滑肌细胞凋亡的研究  

Yes- associated protein I up -regulation inhibits apoptosis of aortic dissection vascular smooth muscle cells

作　　者：刘涛 徐娟 张立 刘华 李亦舒 张群献 张军 郭家龙 Liu Tao;Xu Juan;Zhang Li;Liu Hua;Li Yishu;Zhang Qunxian;Zhang Jun;Guo Jialong(Department of Cardiothoracic Surgery,Taihe Hospital,Hubei University of Medicine,Shiyan 442008,China)

机构地区：[1]十堰市太和医院湖北医药学院附属医院心胸外科,442008

出　　处：《中华实验外科杂志》2018年第10期1834-1838,共5页Chinese Journal of Experimental Surgery

摘　　要：目的观察Yes相关蛋白1（YAP1）的表达在血管平滑肌细胞凋亡和主动脉夹层（AD）发病中的作用。方法建立AD大鼠模型，比较AD模型大鼠血管组织和正常对照大鼠血管组织中细胞凋亡、YAPl的表达。体外培养大鼠胸主动脉血管平滑肌细胞（VSMC），分成4组：Control组、循环拉伸应力加载（Cyclicstretch）组、Cyclicstretch＋plRES2-blank组、Cyclicstretch＋plRES2-YAPl组，检测细胞凋亡率和YAPl、生存素（Survivin）表达。AD模型大鼠分成3组：单纯AD组、Ad．NC注射组、Ad-YAPl注射组，比较YAPl、Survivin的表达，检测血管内细胞凋亡，比较AD形成率和AD直径、长度。结果单纯AD模型组AD形成率为43．1％，AD直径为（6．21±1．13）mm，AD长度为（9．25±1．77）mm；Ad-NC注射组AD形成率为42．3％，AD直径为（6．35±1．22）mm，AD长度为（9．11±1．64）mm；Ad-YAPl注射组AD形成率为28．5％，AD直径为（3．72±0．43）mm，AD长度为（6．42±1．16）mm。与对照组比较，模型大鼠AD血管组织内细胞凋亡明显增加，YAP1的表达明显降低。Cyclicstretch明显诱导VSMC细胞凋亡，过表达YAPl明显上调Survivin的表达，拮抗Cyclicstretch诱导的细胞凋亡。尾静脉注射Ad．YAPl明显上调AD模型大鼠血管组织内YAPI、Survivin的表达，使细胞凋亡明显减少，AD形成率和AD直径、长度也明显降低。结论YAPl的表达降低在促进VSMC细胞凋亡和AD发病中起作用，上调YAPl的表达则可抑制VSMC细胞凋亡和AD的形成。Objective To investigate the role of Yes - associated protein 1 （ YAP1 ） expression in apoptosis of vascular smooth muscle ceils （VSMCs） and pathogenesis of aortic dissection （AD）. Methods AD rat model was established to compare apoptosis and the expression of YAP1 within vascular tissues a- gainst normal controlled rats. In vitro cultured rat thoracic VSMCs were divided into control, cyclic stretch, cyclic stretch ± pIRES2 -blank and cyclic stretch ± pIRES2 -YAP1 groups. Cell apoptosis rate, YAP1 and Survivin expression were measured. AD rats were divided into model, Ad -NC injection, and Ad- YAP1 injection groups for comparing VSMCs apoptosis, AD formation rate, diameter and length. Results The AD rats of AD modle gronpe is 43. 1% [AD diameter is （6. 21 ± 1.13 ） mm, AD length is （9. 25 ± 1.77） mm] ; The AD rats of Ad - NC - injecting groupe is 43.1% [ AD diameter is （6. 21 ± 1. 13） mm, AD length is （9. 25 ± 1.77） mini ; The AD rats of Ad - YAP1 - injecting groupe is 43. 1% [AD diameter is （6. 21 ± 1.13） mm, AD length is （9. 25 ± 1.77 ） mm ]. Compared to control group, AD rats had elevated vascular cell apoptosis, and down - regulated YAP1 expression. Cyclic stretch significantly induced VSMCs apoptosis. YAP1 over- expression up -regulated Surdvin and antagonized cyclic stretch - induced cell apoptosis. Injection of Ad - YAP1 via the tail vein significantly up - regulated YAP1 and Survivin expression, and decreased apoptosis, AD formation rate and AD diameter/length in vascular tissues of rat AD models. Conclusion YAPI down - regulation plays a role in facilitating VSMCs apoptosis and AD pathogenesis. Up - regulation of YAP1 decreases VSMCs apoptosis and AD formation.

关 键 词：Yes相关蛋白1 Hippo-Yes相关蛋白 血管平滑肌细胞 主动脉夹层 脱噬作用 

分 类 号：R285.5[医药卫生—中药学]