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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 investigate the mechanism by which human urotensin (UⅡ) stimulates the secretion of adrenomedullin (Adm) by human vascular endothelial cells (HVECs). Methods HVEC cultured in different concentrations of UⅡ (10-10, 10-9, 10-8 and 10-7mol / L) were stimulated by radioimmunoassay to determine the amount of Adm secreted, and different cell signal transduction blockers (Mitogen-activated protein kinase blocker PD98059, calmodulin-dependent protein kinase inhibitor W7, P38 protein kinase inhibitor SB202190, calcium channel blocker nicardipine, protein kinase C blocker H7 and calcineurin Cyclosporine, an enzyme inhibitor, on its secretion. Results UⅡ could promote the secretion of Adm by HVEC in a time and concentration dependent manner. There was a significant difference between each group and the control group. Both PD98059, W7, SB202190 and nicardipine could inhibit the secretion of Adm induced by UII stimulated HVEC by 67% (P <0.01), 77% (P <0.01), 23% (P <0.05). However, H7 and CsA had no significant effect on the secretion of Adm induced by UII (P> 0.05). Conclusion UⅡ can stimulate the secretion of Adm by HVEC. The mechanism is related to Ca2 +, MAPK, CaMPK and P38 signal transduction pathway.