Walther A, Yilmaz N, Schmidt W, Bach A, Gebhard M M, Martin E, Schmidt H
Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany.
J Crit Care. 2001 Sep;16(3):121-6. doi: 10.1053/jcrc.2001.28975.
During endotoxemia, the early endothelial damage has been shown to be leukocyte independent. Therefore, it was the aim of our study to investigate the role of serotonin in mediating leukocyte-independent microvascular permeability during endotoxemia. Microvascular permeability was determined after inhibition of the L-selectin mediated leukocyte adherence by fucoidin and after inhibition of serotonin effects by the serotonin (5HT)-receptor antagonist methysergide.
In male Wistar rats, leukocyte rolling, leukocyte adherence, and macromolecular leakage were determined in mesenteric postcapillary venules using intravital microscopy. After pretreatment with the serotonin-receptor antagonist methysergide, animals in the FUCO/ETX/5HT-ANT group received a continuous infusion of endotoxin. Animals in the FUCO/ETX group underwent the same procedure but received saline 0.9% instead of methysergide. In both groups, leukocyte adherence was prevented by administration of fucoidin. Animals in the saline group received volume-equivalent saline 0.9%.
In the endotoxin-challenged groups, fucoidin prevented leukocyte rolling and reduced leukocyte adherence to values comparable to saline group. In the FUCO/ETX group, macromolecular leakage increased significantly, starting at 60 minutes. Values in the saline group increased slightly, being significant at 120 minutes, whereas vascular permeability remained unchanged in the FUCO/ETX/5HT-ANT group. Differences in macromolecular leakage between the FUCO/ETX-group versus the FUCO/ETX/5HT-ANT group and the saline group were significant at 120 minutes. Differences in macromolecular leakage between the FUCO/ETX/5HT-ANT group and the saline group were not significant.
The leukocyte-independent endothelial damage during early endotoxemia can be inhibited efficiently by the 5-HT-receptor antagonist methysergide, indicating that serotonin plays an important role in that pathophysiology.
在内毒素血症期间，早期内皮损伤已被证明与白细胞无关。因此，我们研究的目的是探讨血清素在内毒素血症期间介导与白细胞无关的微血管通透性中的作用。在用岩藻依聚糖抑制L-选择素介导的白细胞黏附后，以及在用血清素（5HT）受体拮抗剂美西麦角抑制血清素作用后，测定微血管通透性。
在雄性Wistar大鼠中，使用活体显微镜在肠系膜毛细血管后微静脉中测定白细胞滚动、白细胞黏附和大分子渗漏。在用血清素受体拮抗剂美西麦角预处理后，FUCO/ETX/5HT-ANT组的动物接受内毒素的持续输注。FUCO/ETX组的动物接受相同的程序，但接受0.9%的生理盐水而不是美西麦角。在两组中，通过给予岩藻依聚糖防止白细胞黏附。生理盐水组的动物接受等体积的0.9%生理盐水。
在内毒素攻击组中，岩藻依聚糖阻止了白细胞滚动，并将白细胞黏附减少到与生理盐水组相当的值。在FUCO/ETX组中，大分子渗漏在60分钟时开始显著增加。生理盐水组的值略有增加，在120分钟时显著，而FUCO/ETX/5HT-ANT组的血管通透性保持不变。FUCO/ETX组与FUCO/ETX/5HT-ANT组和生理盐水组之间大分子渗漏的差异在120分钟时显著。FUCO/ETX/5HT-ANT组与生理盐水组之间大分子渗漏的差异不显著。
5-HT受体拮抗剂美西麦角可有效抑制早期内毒素血症期间与白细胞无关的内皮损伤，表明血清素在该病理生理学中起重要作用。
