Effect of ischemia on intestinal permeability of lipopolysaccharides
Effect of ischemia on intestinal permeability of lipopolysaccharides
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DOI：
10.1046/j.1365-2362.2001.00792.x
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发表时间：
2001-02-01
影响因子：
5.5
通讯作者：
Fricker, G
中科院分区：
文献类型：
--
作者：
Drewe, J;Beglinger, C;Fricker, G
本研究采用兔空肠刷状缘膜囊泡（BBMV）、人小肠细胞株Caco-2和大鼠对荧光标记的内毒素（LPS）进行了吸收研究。结果鼠伤寒沙门氏菌（Salmonella typhimurium）的FITC-LPS可被BBMV摄取，并呈剂量依赖性。摄取既不是pH-也不是Na+依赖性的，也不能被未标记的LPS抑制。74.5%的囊泡相关荧光是由于粘附在囊泡膜上，25.5%的囊泡相关荧光被吸收到药物敏感的空间中。LPS在Caco-2细胞单层中的转运呈剂量依赖性。在缺血条件下，即当细胞在缺氧条件下孵育时，渗透速率显著增加。然而，在缺氧和对照细胞之间没有观察到跨上皮电阻的显著差异。乳酸脱氢酶的释放仅与对照细胞略有不同，表明细胞完整性。在原位，肠缺血后，荧光LPS的摄取显着增加，通过荧光激光扫描显微镜观察。结论LPS主要通过被动跨细胞扩散被肠粘膜吸收。在缺血条件下，LPS的渗透性主要通过增强的细胞旁渗透性和上皮破坏而增加。这些发现部分解释了在大血管手术或血栓栓塞期间，临床观察到的肠道暂时性灌注不良后多器官系统衰竭的发展。
Background The enteral absorption of endotoxin (lipopolysaccharide, LPS) was studied in vitro and in vivo.Materials and methods The absorption of fluorescence (FITC) labelled LPS was investigated by uptake studies with rabbit jejunal brush-border membrane vesicles (BBMV), the human intestinal cell line Caco-2 and in rats.Results FITC-LPS from Salmonella typhimurium was taken up into BBMV in a dose-dependent manner. Uptake was neither pH- nor Na+-dependent, nor could it be inhibited by unlabelled LPS. 74.5% of vesicle-associated fluorescence was due to adhesion to the vesicular membranes, 25.5% was taken up into an osmotically-sensitive space. Transport of LPS across Caco-2 cell monolayers was dose-dependent. The permeation rate increased significantly under ischemic conditions, i.e. when the cells were incubated under oxygen-depleted conditions. However, no significant differences in transepithelial electrical resistances were observed between oxygen depleted and control cells. The release of lactate dehydrogenase was only marginally different from control cells, indicating cell integrity. In situ, after gut ischemia, a significantly increased uptake of fluorescent LPS was observed by fluorescence laser scanning microscopy. Conclusion LPS is taken up by the intestinal mucosa, predominantly by passive transcellular diffusion. Under ischemic conditions, the permeability of LPS is increased mainly by an enhanced paracellular permeability and epithelial destruction. The findings partly explain the clinically observed development of multiorgan system failure after temporary malperfusion of the gut during major vascular surgery or thromboembolism.