血小板活化因子受体拮抗剂对内毒素血症幼年大鼠肠黏膜上皮细胞间连接蛋白的影响  

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

作　　者：王丽杰[1] 孙梅[1] 

机构地区：[1]中国医科大学附属盛京医院儿科,辽宁沈阳110004

出　　处：《中国危重病急救医学》2007年第8期477-480,I0002,共5页Chinese Critical Care Medicine

摘　　要：目的观察血小板活化因子（PAF）对内毒素血症大鼠肠黏膜上皮细胞间连接蛋白β-连环蛋白（β-catenin）的影响，探讨PAF受体拮抗剂对肠上皮屏障完整性的保护作用机制。方法采用腹腔注射脂多糖（LPS）制备内毒素血症大鼠模型。于注射LPS前和注射后30min腹腔注射PAF受体拮抗剂BN52021 5mg／kg作为预防组和治疗组；腹腔注射等量生理盐水作为对照组。分别于注射LPS后1．5、3、6、24、48和72h取各组大鼠回肠，用免疫组化及逆转录-聚合酶链反应（RT—PCR）方法检测肠上皮细胞β-catenin蛋白及mRNA表达。结果对照组β-catenin均匀分布于上皮细胞间细胞膜的表面；内毒素组细胞膜表面β-catenin蛋白明显减少，分布不均。免疫组化和RT—PCR检测均可见内毒素组β-catenin蛋白及mRNA水平明显低于对照组，3～24h内降低非常明显（P均〈0．01）；预防组及治疗组变化趋势同内毒素组，各时间点β-catenin蛋白及mRNA水平均较内毒素组高，但差异无显著性。结论PAF在内毒素血症肠黏膜的机械屏障功能损伤中发挥一定作用，预防和治疗性应用PAF受体拮抗剂BN52021可减轻肠损伤。Objective To investigate the effect of platelet activating factor （PAF） on the β- 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 β- catenin protein and β-catenin mRNA expression in intestinal mucosa. Results β- catenin immunohistochemical labeling was evidently observed in the control rats, where β- 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 β- catenin labeling was substantially reduced or irregularly distributed around many cells. The β - catenin contents of optical density average and β - catenin mRNA were obviously decreased in the LPS challenge group compared with that in the control group （P〈0.01）. The content of β- catenin mRNA significantly decreased at 3 to 24 hours （all P〈0. 01）. The levels of β- catenin protein and β- 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. Conclusion 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.

关 键 词：胃肠功能障碍 多器官功能衰竭 血小板活化因子 机械屏障 紧密连接 黏附连接 Β-连环蛋白 幼年 大鼠 

分 类 号：R686[医药卫生—骨科学]