桃红四物汤对蛋白酶激活受体激活诱导血小板释放VEGF和Endostatin的影响  

Effect of Taohong Siwu Decoction on VEGF and endostatin release from platelet by proteinase-activated receptors agonist

作　　者：尹登科[1] 杨晔[1] 尹娟娟[1] 韩岚[1] 许钒[1] 彭代银[1] 

机构地区：[1]安徽中医学院药学院安徽省中药研究与开发重点实验室,安徽合肥230031

出　　处：《中成药》2012年第9期1631-1635,共5页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金项目(81073091);安徽省高等学校自然科学基金项目(KJ2011A189)

摘　　要：目的考察桃红四物汤对蛋白酶激活受体(PARs)激动剂诱导人血小板聚集、释放血管内皮生长因子(VEGF)和内皮抑素(endostatin)以及释放液对内皮细胞增殖的作用。方法人富血小板血浆和不同质量浓度的桃红四物汤(0.5～2.5 mg/mL)孵育5 min后,加入PAR1选择性激动剂(SFLLRN-NH2,10μmol/L)或PAR4选择性激动剂(AYPGKF-NH2,200μmol/L)或凝血酶(1 U/mL),血小板聚集仪测定血小板聚集,ELISA测定血小板离心后上清中VEGF和endostatin,MTT测定释放液对内皮细胞增殖的作用。结果桃红四物汤在质量浓度0.5～2.5 mg/mL剂量依赖性的抑制凝血酶和PAR1-AP诱导的血小板聚集,但是对PAR4-AP诱导的血小板聚集没有显著的抑制作用;2.5 mg/mL桃红四物汤可抑制PAR1-AP诱导血小板释放VEGF以及PAR4-AP诱导endostatin释放;对PAR1-AP诱导释放液引起内皮细胞的增殖具有抑制作用,而对PAR4-AP诱导的释放液引起内皮细胞增殖减少具有促进作用。结论桃红四物汤抑制PAR1-AP诱导的血小板聚集,调节血小板释放VEGF和endostatin以及内皮细胞增殖可能是其发挥活血化瘀作用的机制之一。AIM To investigate the effect of Taohong Siwu Decoction on proteinase-activated receptors activating peptides（PAR1-AP and PAR4-AP） induced platelet aggregation and the release of VEGF and endostatin on endothelial cell proliferation.METHODS After five min incubation of human platelet-rich plasma with Taohong Siwu Decoction（0.5-2.5 mg/mL）,PAR1-AP（SFLLRN-NH2,10 μmol/L） or PAR4-AP（AYPGKF-NH2,200 μmol/L） or thrombin（1 U/mL） were added,and platelet aggregation was determined by aggregometer.VEGF and endostatin released by activated-platelet were assayed with ELISA kits,and the effect of these secretions of platelet on endothelial cell proliferation was detected by MTT method.RESULTS Taohong Siwu Decoction（0.5-2.5 mg/mL） inhibited thrombin and PAR1-AP induced platelet aggregation in dose-depended manner.However,it did not exhibit significantly inhibition on PAR4-AP induced platelet aggregation.Taohong Siwu Decoction（2.5 mg/mL） inhibited platelet release of VEGF induced by PAR1-AP and endostatin induced by PAR4-AP.Pretreated platelets with Taohong Siwu Decoction（2.5 mg/mL） also inhibited the PAR1-AP activated platelet secretions induced endothelial cell proliferation,and promoted decrease of PAR4-AP activated platelet secretions in endothelial cell proliferation.CONCLUSION The inhibiting effect of Taohong Siwu Decoction on PAR1-AP induced platelet aggregation,and the regulation on VEGF and endostatin released from platelet and endothelial cell proliferation may play the role in its effect on promoting blood circulation and removing blood stasis.

关 键 词：桃红四物汤 蛋白酶激活受体 血小板 血管内皮生长因子 内皮抑素 

分 类 号：R285.5[医药卫生—中药学]