首页|Tumor necrosis factor alpha increases intestinal permeability in mice with fulminant hepatic failure
Tumor necrosis factor alpha increases intestinal permeability in mice with fulminant hepatic failure
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NETL
NSTL
万方数据
维普
AIM:To determine the effect of tumor necrosis factor alpha (TNF-α） on intestinal permeability (IP) in mice with fulminant hepatic failure (FHF),and the expression of tight junction proteins.METHODS:We selected D-lactate as an index of IP,induced FHF using D-galactosamine/lipopolysaccharide and D-galactosamine/TNF-α,assessed the results using an enzymatic-spectrophotometric method,transmission electron microscopy,immunohistochemistry,Western blotting and real-time quantitative polymerase chain reaction.The effect of the administration of antiTNF-α immunoglobulin G (IgG) antibody,before the administration of D-galactosamine/lipopolysaccharide,on TNF-α was also assessed.RESULTS:IP was significantly increased in the mouse model of FHF 6 h after injection (13.57 ± 1.70 mg/L,13.02 ± 1.97 mg/L vs 3.76 ± 0.67 mg/L,P =0.001).Electron microscopic analysis revealed tight junction (TJ) disruptions,epithelial cell swelling,and atrophy of intestinal villi.Expression of occludin and claudin-1 mRNA was significantly decreased in both FHF models (occludin:0.57 ± 0.159 fold vs baseline,P =0.000;claudin-1:0.3067±0.1291 fold vs baseline,P =0.003),as were the distribution density of proteins in the intestinal mucosa and the levels of occludin and claudin-1 protein (occludin:0.61 ± 0.0473 fold vs baseline,P =0.000; claudin-1:0.6633 ± 0.0328 fold vs baseline,P =0.000).Prophylactic treatment with antiTNF-α IgG antibody prevented changes in IP (4.50 ±0.97 mg/L vs 3.76 ± 0.67 mg/L,P =0.791),intestinal tissue ultrastructure,and the mRNA levels of occludin and claudin-1 expression (occludin:0.8865 ± 0.0274fold vs baseline,P =0.505; claudin-1:0.85 ± 0.1437fold vs baseline,P =0.1),and in the protein levels (occludin:0.9467 ± 0.0285 fold vs baseline,P ＞ 0.05;claudin-1:0.9533 ± 0.0186 fold vs baseline,P =0.148).CONCLUSION:Increased in IP stemmed from the downregulation of the TJ proteins occludin and claudin-1,and destruction of the TJ in the colon,which were induced by TNF-α in FHF mice.
NETL
NSTL
万方数据
维普
