Haller H, Hempel A, Homuth V, Mandelkow A, Busjahn A, Maasch C, Drab M, Lindschau C, Jüpner A, Vetter K, Dudenhausen J, Luft F C
Franz Volhard Clinic, Berlin, Germany.
Lancet. 1998 Mar 28;351(9107):945-9. doi: 10.1016/S0140-6736(05)60605-8.
Oedema and vascular leakage play a part in the pathogenesis of pre-eclampsia. We tested the hypothesis that serum from pre-eclamptic patients increases endothelial-cell permeability and examined possible signal-transduction pathways.
We studied eight patients with pre-eclampsia, eight normotensive pregnant women, eight non-pregnant women, five pregnant patients with pre-existing hypertension, and four hypertensive non-pregnant women. Cultured human umbilical-vein endothelial-cell monolayers were used and permeability was measured by albumin flux. The part played by protein kinase C (PKC) signalling was examined by down-regulation with phorbol ester and with the inhibitors Goe 6976 and staurosporine. PKC isoforms were assessed by western blot and confocal microscopy. Antisense oligodesoxynucleotides (ODN) were used to test for specific PKC isoforms.
Serum from pre-eclamptic women increased endothelial permeability significantly (by 100%, p<0.01). The change in permeability decreased rapidly after delivery. Serum from normotensive pregnant women and non-pregnant women had no effect. Permeability was not influenced by serum from patients with essential hypertension or pregnant patients with pre-existing hypertension. Serum from pre-eclamptic patients induced a translocation of PKC isoforms alpha and epsilon within the cells. Goe 6976 and staurosporine (10(-8) mol/L) inhibited the increase in permeability induced by serum from pre-eclamptic patients. Down-regulation of PKC alpha and, to a lesser extent, PKC epsilon by antisense ODN also inhibited the pre-eclampsia-induced permeability increase.
Serum from pre-eclamptic patients contains a factor or factors that increase endothelial-cell permeability. The effect of pre-eclamptic serum may be mediated by PKC alpha and epsilon.
水肿和血管渗漏在子痫前期的发病机制中起作用。我们检验了子痫前期患者血清会增加内皮细胞通透性这一假说，并研究了可能的信号转导途径。
我们研究了8名单纯性子痫前期患者、8名血压正常的孕妇、8名非孕女性、5名孕前即患有高血压的孕妇以及4名高血压非孕女性。使用培养的人脐静脉内皮细胞单层，通过白蛋白通量测量通透性。用佛波酯以及抑制剂Goe 6976和星形孢菌素下调蛋白激酶C（PKC）信号，以研究其作用。通过蛋白质印迹法和共聚焦显微镜评估PKC亚型。使用反义寡脱氧核苷酸（ODN）检测特定的PKC亚型。
子痫前期女性的血清显著增加了内皮通透性（增加了100%，p<0.01）。分娩后通透性的变化迅速降低。血压正常的孕妇和非孕女性的血清无此作用。原发性高血压患者或孕前即患有高血压的孕妇的血清对通透性无影响。子痫前期患者的血清诱导细胞内PKC亚型α和ε易位。Goe 6976和星形孢菌素（10⁻⁸ mol/L）抑制了子痫前期患者血清诱导的通透性增加。反义ODN对PKCα以及程度较轻的PKCε的下调也抑制了子痫前期诱导的通透性增加。
子痫前期患者的血清含有一种或多种增加内皮细胞通透性的因子。子痫前期血清的作用可能由PKCα和ε介导。
