尾加压素刺激血管内皮细胞分泌肾上腺髓质素的机制  

Mechanism of urotensin Ⅱ-stimulated adrenomedullin secretion in human vascular endothelial cells

作　　者：石向东[1] 李志梁[1] 吴宏超[1] 王同汉[1] 傅强[1] 严全能[1] 唐朝枢[2] 

机构地区：[1]南方医科大学珠江医院心内科,广东广州510282 [2]北京大学第一医院心血管研究所,北京100034

出　　处：《第一军医大学学报》2005年第7期791-793,共3页Journal of First Military Medical University

基　　金：国家重大发展基础研究项目(973)子课题(G200056905)~~

摘　　要：目的研究人尾加压素(UⅡ)刺激人血管内皮细胞(HVEC)分泌肾上腺髓质素(Adm)的机制。方法以不同浓度的UⅡ(10-10、10-9、10-8、10-7mol/L)刺激培养的HVEC,放射免疫法测定其分泌Adm的量,以及不同的细胞信号转导阻滞剂(丝裂素活化蛋白激酶阻断剂PD98059、钙调素依赖性蛋白激酶阻断剂W7、P38蛋白激酶抑制剂SB202190、钙通道阻断剂nicardipine、蛋白激酶C阻断剂H7及钙调神经磷酸酶抑制剂环孢霉素)对其分泌的影响。结果UⅡ可促进HVEC分泌Adm,且呈时间和浓度依赖性。各组与对照组之间有显著差别。PD98059、W7、SB202190及nicardipine均能抑制UⅡ刺激的HVEC对Adm的分泌,其抑制率分别为67%(P<0.01)、77%(P<0.01)、23%(P<0.05)、24%(P<0.05)。而H7、CsA对UⅡ刺激HVEC分泌Adm无显著影响(P>0.05)。结论UⅡ能刺激HVEC分泌Adm,其机制与Ca2+、MAPK、CaMPK及P38信号转导通路介导有关。Objective To study the mechanism of urotensin Ⅱ( UⅡ)-stimulated adrenomedullin secretion in human vascular endothelial cells.Methods In cultured human vascular endothelial cells (HEVCs),different concentrations of UⅡ was used to stimulate the secretion of Adm,and different inhibitors were used to study the changes in the secretion after block of different signal transduction pathways.The contents of Adm in the medium were detected with radioimmunoassay.Results UⅡ-stimulated Adm secretion in the HEVCs in a time- and concentration-dependent manner.Adm contents of the treatment groups were comparable with that of the control group (P<0.05 ),and the secretion of Adm could be inhibited by the inhibitor of extracellular signal-regulated protein kinases (PD098059),p38 kinase inhibitor (SB202190),calmodulin inhibitor (W7) and Ca2+ inhibitor (nicardipine)(P<0.05),but calcineurin inhibitor and protein kinase C inhibitor (H7) had no such effect (P>0.05).Conclusion Ca2+,MAPK,CaM-PK and p38 signal transduction pathways may play major roles in UⅡ-stimulated cecretion of Adm in HVECs.

关 键 词：内皮细胞 尾加压素 肾上腺髓质素 信号转导 

分 类 号：R33[医药卫生—人体生理学]