内毒素上调血管内皮细胞11β-HSD2基因的表达

Mechanism of 11β-HSD2 gene expression up-regulated by endotoxin in vascular endothelial cells

目的 探讨内毒素对血管内皮细胞内11β羟基类固醇脱氢酶2 (11βHSD2 )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 聚合酶链反应,测定血管内皮细胞在不同剂量内毒素作用时11βHSD2mRNA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11βHSD2mRNA的量。结果 内毒素1 0、10、2 0、5 0、10 0 μg/L与血管内皮细胞共培养2 4h后11βHSD2mRNA/βactinmRNA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11βHSD2mRNA水平增高。结论 内毒素可诱导11βHSD2基因转录增强,激活p3 8MAPK可能是一种重要机制。

Objective To investigate effects of endotoxin on 11β-HSD2 gene transcription in vascular endothelial cells to observe the role of p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Methods The effects of endotoxin in the presence or absence of p38 MAPK specific inhibitor SB203580 on the transcription of 11β-HSD2 in vascular endothelial cells was evaluated by reverse transcription DNA polymerase chain reaction. Results Treatments of endotoxin (1.0, 10, 20, 50, 100 μg/ L) for 24 h increased the ratios of 11β-HSD2mRNA/β-actin mRNA in vascular endothelial cells. The induction of 11β-HSD2 mRNA by endotoxin could be inhibited partially by 10 mmol/ L SB203580. Conclusion Endotoxin stimulated the transcription of 11β-HSD2 gene in vascular endothelial cells. The activation of p38 MAPK might be an important mechanism of 11β-HSD2 gene induced by endotoxin.