摘要：

AIM:To determine the in vivo effects of phagocytic blockade of Kupffer cell(KC)on the release of proinflammatory cytokines in small intestinal lesion and on the integrity of intestinal tract by using gadolinium chloride(GdCl3)during early endotoxemia.METHODS:Wistar rats were divided into three groups:GropA,rats were injected with endotoxin(E.coliO111:B4,adose of 12mg·kg^-1)only;GroupB,rats were pretreated intravenously with 25mg of GdCl3per kg24hare given endotoxin;and Group C,sham operation only.All animals were sacrificed 4h after endotoxin injecton.In portion of the rats of three groups.bile duct was cannulated,which the bile was collected externally.Morphological changes of ileum were observed under light microscopy and electronic microscopy.The KC were isolated rfrom rats by collagenase perfusion and inKC,expression of TNF-αand IL-6mRNA were determined by RT-PCRanalysis.Plasma and bile TNF-αandIL-6Levels were determined by enzyme-linked immunosorbent assay(EISA)>RESULTS:In group A,there were neutrophil infiltration and superficial epitelial necrosis of the ilealvvilli,sloughing of mucosal epithelium.and disappear ance of somevilli.In groupB.the ileal mucosal damage was much reduced.which in groupC,no significant morphological changes were seen,GdCl3pretreatment decreased significantly the expression of TNF-αand IL-6mRNA ingroupB(4.32±0.47and4.05±0.43)when compared to groupA(9.46±1.21and9.04±1.09)(P<0.05).There was no significant expression of TNF-αand IL-6mRNA in groupC(1.03±0.14and10.4±0.13).In rats of groupA,the levels of TNF-αand IL-6in bile and plasma were 207±29ng·L^-1,1032±107ng·L^-1,213±33ng·L^-1,and 1185±127ng·L^-1,respectively.In groupB,they were113±18ng·L^-1,repectively.In groupC,they were 67±10ng·L^-1,72±13ng·L^-1,109±18ng·L^-1,and 118±22ng·L^-1respectively.There were significant difference between the three group(P<0.05).CONCLUSION:KC release cytokinesTNF-αand IL-6causing damage to the integrity of intestinal epithelium and play a crucial role in the initiation and progression of intestinal mucosal damage during early endotoxemia.

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