内毒素上调血管内皮细胞肾上腺髓质素基因及其机制探讨

Mechanism of adrenomedullin gene expression upregulated by endotoxin in vascular endothelial cells

目的 :探讨内毒素对血管内皮细胞肾上腺髓质素 (ADM)mRNA的影响 ,以及p3 8丝裂原活化蛋白激酶 (p3 8MAPK)在其中所起的作用。方法 :应用逆转录 -巢式聚合酶链反应 ,测定血管内皮细胞株ECV3 0 4在不同剂量内毒素作用时ADMmRNA的量以及采用p3 8MAPK特异性抑制剂SB2 0 3 5 8( 10mmol/L)抑制p3 8MAPK后ADMmR NA的量。结果 :内毒素 0 1、1 0、10、5 0、10 0 μg/L与ECV 3 0 4共培养 2 4h后ADMmRNA/ β -actinmRNA均不同程度高于正常培养水平 ,而SB2 0 3 5 80抑制p3 8MAPK后可部分抑制内毒素引起的ADMmRNA水平增高。结论 :内毒素可诱导ADM基因转录增强 ,激活p3 8MAPK可能是一种重要机制。

AIM: To investigate effect of endotoxin on adrenomedulin(ADM) gene transcription in vascular endothelial cells. The role of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway was also observed.METHODS: The effect of endotoxin in the presence or absence of p38 MAPK specific inhibitor SB203580 on the transcription of ADM in vascular endothelial cells ECV304 was evaluated by reverse transcription nest DNA polymerase chain reaction. RESULTS: Treatments of endotoxin (0.1, 1.0, 10, 50, 100 μg/L) for 24 h increasea the ratios of ECV 304 ADM mRNA/β actin mRNA. The induction of ADM mRNA by endotoxin could be inhibited partially by 10 mmol/L SB203580.CONCLUSION: Endotoxin stimulated the transcription of ADM gene in vascular endothelial cells. The activation of p38 MAPK might be an important mechanism of ADM gene induced by endotoxin.