[Effect of platelet activating factor receptor antagonist on the tight junction associated protein between the epithelial cells of intestinal mucosa during endotoxemia in young rats].
OBJECTIVE
To investigate the effect of platelet activating factor (PAF) on the beta-catenin between the epithelial cells of intestinal mucosa during endotoxemia in rats, and to explore the mechanism of prospective effect of PAF receptor antagonist on intestinal epithelial barrier integrity.


METHODS
Rat model of endotoxemia was reproduced by intraperitoneal injection of lipopolysaccharide (LPS). Rats receiving PAF receptor antagonist BN52021 5 mg/kg before and 30 minutes after LPS injection were taken as pretreatment group and treatment group, respectively. In control group, rats received normal saline instead of LPS. The ileum tissue was harvested at 1.5, 3, 6, 24, 48 and 72 hours after LPS injection. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine beta-catenin protein and beta-catenin mRNA expression in intestinal mucosa.


RESULTS
beta-catenin immunohistochemical labeling was evidently observed in the control rats, where beta-catenin labeling appeared mainly in the shape of lines defining the pericellular spaces between cells. This was in contrast to what was observed in rats after LPS challenge, where beta-catenin labeling was substantially reduced or irregularly distributed around many cells. The beta-catenin contents of optical density average and beta-catenin mRNA were obviously decreased in the LPS challenge group compared with that in the control group (P<0.01). The content of beta-catenin mRNA significantly decreased at 3 to 24 hours(all P<0.01). The levels of beta-catenin protein and beta-catenin mRNA in pretreatment group and treatment group were higher than those in the LPS group at each time point but without statistically significant difference.


CONCLUSIONS
PAF plays a role in the injury to intestinal mechanical barrier function during endotoxemia. Preventive and remedial use of PAF receptor antagonist BN52021 may alleviate intestinal injury.
Wang
Li-jie
LJ
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China. wlj682002@yahoo.com.cn
Sun
Mei
M
D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D046934:Ginkgolides / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D046934:Ginkgolides; D007783:Lactones; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D051176:beta Catenin; C039351:platelet activating factor receptor; C045856:ginkgolide B