尾加压素Ⅱ促血管内皮细胞分泌肾上腺髓质素的作用

目的研究人尾加压素（human urotensinⅡ,HUⅡ）对人血管内皮细胞（human vascular endothelial cells,HVEC）分泌肾上腺髓质素（adrenomedullin,ADM）的影响及可能机制。方法不同浓度的HUⅡ（10^-10～10^-7mol／L）刺激培养的HVEC,用放射免疫法测定其分泌ADM的量,并加入不同细胞信号转导分子阻滞剂以测定其对分泌的影响。结果HUⅡ呈时间和浓度依赖性的增加HVEC分泌ADM。细胞外信号调节激酶抑制剂PD98059及钙调素依赖性蛋白激酶抑制剂W7、P38蛋白激酶抑制剂SB202190及钙通道阻滞剂nicardipine均能抑制HUⅡ刺激的HVEC对ADM的分泌,其抑制率分别为68％（P〈0．01）、78％（P〈0．01）及24％（P〈0．05）、25％（P〈0．05）;蛋白激酶C抑制剂H7、钙调神经磷酸酶抑制剂环孢霉素（CsA）对HUⅡ刺激HVEC分泌ADM无明显影响。结论HUⅡ能刺激HVEC分泌ADM,其作用可能与Ca^2＋、ERKs、CaM PK及P38介导的信号转导通路有关。

Effect of urotensin II on secretion of adrenomedullin from human vascular endothelial cells

OBJECTIVE: To study the effect of human urotensin II (HU II) on secretion of adrenomedullin (ADM) from human vascular endothelial cells (HVEC) and its mechanism. METHODS: In cultured HVEC, different concentrations of HUII were used to stimulate the ADM secretion from HVEC, and the inhibitors of different signal transduction pathway were used to investigate their effects on ADM secretion. The contents of ADM in medium were determined by radio immunoassay. RESULTS: HUII stimulated secretion of ADM from HVEC in a time-dependent and concentration-dependent manner. The contents of ADM in the experiment groups were changed compared with that in control group (P < 0.05). The increase of ADM could be inhibited by inhibitor of extracellular singal-regulated protein kinase (PD(98059)), inhibitor of P38 kinase (SB(202190)), inhibitor of calmodulin (W(7)) and inhibitor of Ca(2+) (nicardipine) (P < 0.05). The inhibition ratio in those groups was 68%, 78%, 24% and 25% respectively. But the inhibitor of Calcineurin (CaN) and inhibitor of protein kinase C (H(7)) had no influence on the secretion of ADM from HVEC (P > 0.05). CONCLUSION: The stimulated effect of HUII on the ADM secretion from HVEC may be mediated by Ca(2+), ERKs, CaM-PK and P38 signal transduction pathways.