剪应力和压力对家兔离体动脉血管段内皮细胞分泌PAI-1、t-PA、vWF功能的联合效应  

Joint Effects of Shear Stress and Pressure on Secretion of PAI-1,t-PA and vWF in Endothelial Cells of Isolated Arterial Vessels in Rabbits

作　　者：殷小杰[1] 曹军[1] 郝杨阳 贡磊磊 王岚[1] 王薇 梁日欣[1] 廖福龙[1] YIN Xiaojie;CAO Jun;HAO Yangyang;GONG Leilei;WANG Lan;WANG Wei;LIANG Rixin;LIAO Fulong(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]首都医科大学中医药学院,北京100069

出　　处：《中国药物警戒》2018年第8期456-461,共6页Chinese Journal of Pharmacovigilance

基　　金：国家自然基金面上项目(81473548):活血化瘀抗动脉粥样硬化与血栓形成的剪应力效应机理

摘　　要：目的研究家兔离体动脉血管段在不同剪应力和不同平均压力组合作用下分泌PAI-1、t-PA、vWF水平及基因表达水平的规律。方法手术分离实验家兔腹主动脉、颈总动脉,采用离体血管灌流装置,对家兔动脉血管实施不同剪应力(范围2~22 dyn·cm^(-2))和不同压力(范围9.0~48.4 mm Hg);放免法测定灌流剪切液中vWF、PAI-1、t-PA的含量;RT-PCR法测定应力加载动脉血管vWF,PAI-1和t-PA基因的表达水平。结果低水平剪应力联合低压力,高水平剪应力联合高压力,中等水平剪应力联合中等压力3个组合作用于内皮细胞,可抑制PAI-1的表达;中等水平剪应力和中等压力联合作用,可促进t-PA的表达;高水平的血流剪应力与高压力联合作用,可抑制vWF的表达。结论离体家兔动脉血管灌流时,血流剪应力与压力联合作用可影响血管内皮细胞PAI-1,t-PA,vWF的分泌,其作用机制则与应力调节相应基因的表达有关。Objective To study the joint effects of shear stress and pressure on secretion and expression of PAI-1,t-PA,vWF in endothelium of isolated rabbit vessel. Methods Ex vivo arterial perfusion system was used to establish the rabbit artery perfusion model under different flow conditions of shear stress（2-22 dyn·cm^-2） and different pressure（9.0-48.4 mm Hg）.The perfusate was collected to determine the level of vWF, PAI-1 and t-PA by using radioimmunoassay. And the expression level of vWF m RNA,PAI-1 m RNA and t-PA m RNA was measured by real-time PCR method. Results The low shear stress combined with the low normal pressure, the medium shear stress combined the medium normal pressure and the higher shear stress with the higher normal pressure decreased the level of PAI-1 in perfusate, and meanwhile up-regulated the gene expression of PAI-1. The medium shear stress combined the medium normal pressure increased the level of t-PA in perfusate and up-regulated expression of t-PA. The high shear stress combined withthe high normal pressure decreased the level of vWF. Conclusion In isolated blood vessel model loaded by shear stress, shear stress and pressure could exert a joint effects on endothelial functions, which may be related with gene expression of vWF, PAI-1 and t-PA, which indicated that the physical and pathological importance deserves further investigation on the quantitative relationship between biological effects and shear stress.

关 键 词：剪应力 压力 血管内皮细胞 基因表达 家兔 

分 类 号：R965[医药卫生—药理学]