Abelson非受体酪氨酸激酶及肌动蛋白动态细胞骨架结构在夹层主动脉组织中的变化

Association of abelson non-receptor tyrosine kinase and actin cytoskeleton dynamics with aortic dis- section

目的探讨Abelson非受体酪氨酸激酶（c—Abl）及肌动蛋白骨架结构与主动脉夹层的关系。方法夹层主动脉标本获取自行A型主动脉夹层手术的患者，分为高血压组（／7,=9）和正常血压组（n=15），对照组来自移植心脏的主动脉标本（n=8）。bax蛋白与bcl-2蛋白比值评估凋亡水平。纤维化肌动蛋白（F．actin）和球状单体肌动蛋白（G．actin）含量比值分析肌动蛋白细胞骨架动态结构。免疫印迹分析测量c．Abl和磷酸化c．Abl蛋白水平。结果bax蛋白与bcl-2蛋白比值在正常对照组，高血压夹层组和正常血压夹层组内分别为（0．97±0．02、2．45±0．06、2．30±0．12），夹层组中比值升高（P〈0．叭）。F—actin与G—actin含量比值分别为（1．53±0．03、3．00±0．03、2．72±0．04），夹层组中比值升高（P〈0．01）。C．Abl蛋白含量比值分别为（0．12±0．01、0．36±0．01、0．41±0．02），夹层组中含量增加（P〈0．01）；磷酸化c—Abl蛋白含量比值分别为（0．0047±0．0003、0．023±0．001、0．021±0．001），夹层组中含量增加（P〈0．01）。上述数据在高血压组与正常血压组比较差异无统计学意义（P〉0．05）。结论c-Abl及其激活与主动脉夹层的相关性。C-Abl及其激活可能通过调节血管平滑肌细胞的凋亡和肌动蛋白细胞骨架结构来参与主动脉夹层的发生和发展。

Objective To determine the possible relationship between abelson non-receptor tyro- sine kinase （c-Abl） and aortic dissection. Methods Aortic specimens were obtained from patients under- going aortic replacement surgery for type A aortic dissection with high blood pressure （ n = 9, HBP-AD group） and with normal blood pressure （ n = 15, NBP-AD group）, along with control donors dying of cau- ses unrelated to aortic disease （ n = 8, cpmtrol group, collected during heart transplantation）. Apoptosis was also assessed by bax/bcl-2. Filamentous actin （F-actin） and global actin （G-actin） were tested as a measure of actin cytoskeleton dynamics. Western blotting was performed to evaluate c-Abl and phosphoryla- ted c-Abl protein levels. Results bax/B lymphocytes/leukemia-2 （bcl-2） were elevated in aortic tissue from patients with aortic dissection as compared with those in controls （ Controls ： 0.97 ± 0. 02 ; HBP-AD ： 2. 45 _± 0.06, P 〈 0.01 vs controls ; NBP-AD ： 2. 30 ± 0. 12, P 〈 0. 01 vs Controls）. Actin polymerization was increased in aortic tissue （ Controls ： 1.53 ±0. 03 ; HBP-AD ： 3.00 ± 0.03, P 〈 0. 01 vs Controls ; NBP-AD： 2.72±0.04,P〈0.01 vs Controls）. C-Abl （Controls： 0.12±0.01; HBP-AD： 0.36±0.01, P 〈0. 01 vs Controls; NBP-AD： 0. 41 ±0. 02,P 〈0. 01 vs Controls） and phosphorylated c-Abl protein lev- els （ Controls： 0. 0047 ±0. 0003 ; HBP-AD： O. 0230 ±0. O010,P 〈0. 01 vs Controls; NBP-AD： 0. 0210 ± 0. 0010,P〈0. 01 vs Controls） wer also elevated. However, there was no significant difference between HBP-AD group and NBP-AD group in all data （ P 〉 0. 05 ）. Conclusion c-Abl is associated with aortic dissection, probably by regulating apoptosis and the actin cytoskeleton, c-Abl could be a potential target of prevention and treatment for aortic dissection.