力-化学耦合作用在血管内皮细胞迁移中的作用及其力学生物学机制  

Mechanical-chemical interaction and its mechanobiological mechanism on the migration of endothelial cells

作　　者：黄先亮[1] 刘肖珩[1] 曾烨[1] 赖怡[1] 沈阳[1] 毛斌[1] 高亭[1] 俞燚[1] 

机构地区：[1]四川大学华西基础医学与法医学院生物医学工程研究室,成都610041

出　　处：《医用生物力学》2010年第5期321-327,共7页Journal of Medical Biomechanics

基　　金：国家自然科学基金资助项目(10972148,10772127);四川省青年科技基金(06ZQ026-009);教育部新世纪优秀人才支持计划(NCET-06-0789)

摘　　要：目的研究力学与化学因素的耦合在内皮细胞迁移过程中的作用以及其中的力学生物学机制。方法在不同大小剪应力下分别用RT-PCR、Western blot以及免疫荧光的方法检测内皮细胞CXCR1和CXCR2的表达变化;用anti-IL8RA和anti-IL8RB拮抗CXCR1和CXCR2,在剪应力作用下观察内皮细胞迁移情况;采用脂质体包绕法分别将Rac1及RhoA的野生型、活化型和抑制型3种质粒转染入内皮细胞,将转染了Rac1的3种质粒的细胞分别施加力学(剪应力)和化学(IL-8)刺激,对转染了RhoA的3种质粒的细胞施加化学刺激,检测以上条件下内皮细胞迁移情况。结果 CXCR1和CXCR2作为新型力学感受器参与调节内皮细胞迁移;Rac1与RhoA的高表达能促进内皮细胞迁移,反之,内皮细胞迁移被抑制。结论 IL-8Rs(CXCR1、CXCR2)、Rac1、RhoA是将力学、化学信号进行"耦合"的关键信号分子。Objective To elucidate the mechanical chemical interaction and its mechanobiological mechanism on the migration of endothelial cells.Method RT-PCR,Western blot and immunofluorescence were applied to detect the expression of CXCR1 and CXCR2 and their distributions under three levels of shear stress;anti-IL8RA and anti-IL8RB were used to inhibit CXCR1 and CXCR2 to evaluate endothelial cell migration under shear stress;ECs were transfected to obtain the wild type Rac1（Rac1WT） or RhoA（RhoAWT）,the constitutively active forms of Rac1（Rac1Q61L） or RhoA（RhoA63L）,and the dominant negative forms of Rac1（Rac1T17N） or RhoA（RhoA188A） respectively,with lipofectamine 2000 reagent.ECs transfected with three plasmids of Rac1 were exposed to three levels of shear stress and IL-8,respectively;ECs transfected with three plasmids of RhoA were stimulated by IL-8.Results CXCR1 and CXCR2 are novel mechano sensors mediating laminar shear stress induced endothelial cell migration.High expression of Rac1 and RhoA can promote EC migration,while their low expression inhibits EC migration.Conclusions CXCR1,CXCR2,Rac1 and RhoA are critical signaling molecules in mechanical chemical interaction of EC migration.

关 键 词：内皮细胞迁移 剪应力 力学生物学 刺激 

分 类 号：R318.01[医药卫生—生物医学工程]