细菌内毒素对血管内皮细胞ERK1/ERK2和P38分裂原激活的蛋白激酶磷酸化的影响

ACTIVATION OF ERK1/ERK2 AND P38MAPK PHOSPHORYLATION IN VASCULAR ENDOTHELIAL CELLS INDUCED BY LPS

研究细菌内毒素（ＬＰＳ）对血管内皮细胞的直接损伤机制，有助于了解内毒素血症对血管内皮的直接损害机制及其在多脏器损害中的作用。本研究通过观察ＬＰＳ刺激血管内皮细胞后，对内皮细胞中细胞外信号调节激酶（ＥＲＫ）１／ＥＲＫ２和Ｐ３８分裂原激活的蛋白激酶（ＭＡＰＫ）磷酸化的影响，发现ＬＰＳ（１ｍｇ／Ｌ）直接作用内皮细胞后Ｐ３８ＭＡＰＫ磷酸化程度明显增强，并与ＬＰＳ剂量有明显依赖关系。２．５ｍｇ／ＬＬＰＳ刺激后，Ｐ３８ＭＡＰＫ磷酸化在１５ｍｉｎ反应最强，３０ｍｉｎ后减弱，约６０ｍｉｎ后消失。而ＥＲＫ１和ＥＲＫ２的磷酸化在１５～３０ｍｉｎ明显，６０ｍｉｎ减弱，其总强度不如Ｐ３８ＭＡＰＫ。由此证明，ＬＰＳ直接作用内皮细胞后其信号可以通过跨膜传导，将ＭＡＰＫ激活，并可能引起细胞核内的基因转录和胞浆内功能蛋白的磷酸化，导致血管内皮细胞的多种功能变化。

To study the mechanism of direct injuring effect of LPS on vascular endothelial cells(VECs) is helpful to understand endotoxemia's role in multi organ failure. In this paper, LPS was used to stimulate VECs(RF/6A135), and its effects on ERK1/ERK2 and P38MAPK phosphorylation were observed. After VEC were directly stimulated VECs by LPS (1 μg/ml), we found that p38MAPK phosphorylation was remarkable increased, and it was concentration depended. P38MAPK phosphorylation reached a peak at 15 min and then weakened after 30 min with the stimulation of 2 5μg/ml LPS. ERK1/ERK2 phosphorylation was increased during 15￣30 min and weakened after 60 min, the phosphorylation intensity of ERK1/ERK2 was less than p38MAPK's. The data suggest that direct stimulation of LPS evokes VECs MAPK's phosphorylation by signal transmembrane transduction, and it may elicit nucleolus gene transcription and cytoplasma functional proteins phosphrylation, leading to alteration in biological function of VEC.