摘要目的 观察卡巴胆碱对脓毒症大鼠肠屏障功能的保护作用.方法 将32只雄性SD大鼠随机分为4组:对照组、脓毒症组、卡巴胆碱组、α-银环蛇毒素(α-BGT)组.腹腔注射脂多糖(LPS)后6h取距回盲瓣10 cm处回肠组织,用于紧密连接蛋白-1(ZO-1)、核转录因子-κB(NF-κB)、核转录因子抑制蛋白(IκB)和病理学检查.结果 与脓毒症大鼠比较,卡巴胆碱组回肠组织ZO-1移位减少、含量增加(0.75 ±0.12,P＜0.05),NF-κB含量减少(0.56 ±0.09.P＜0.05),回肠组织病理学损伤明显减轻(1.25±0.05,P＜0.05).经α-BGT拮抗后,卡巴胆碱保护效应被抵消.结论 卡巴胆碱对脓毒症大鼠肠屏障功能有保护作用,其机制可能与激活胆碱能抗炎通路有关.

abstractsObjective To investigate the effects of carbachol on lipopolysaccharide (LPS)-induced intestinal barrier breakdown.Methods Male Sprague-Dawley rats were randomly divided into four groups (n =8 per group):control group,sepsis group,carbachol group,α-bungarotoxin (α-BGT) group.Rats were sacrificed at 3 h after LPS administration for biochemical studies and histological examination.The localization and expression of zonula occludens-1 (ZO-1) and the activation of nuclear factor-kappa B (NF-κB),expression of IκB,and pathologic changes of ileum were examined.Results LPS challenge significantly induced redistribution of ZO-1 protein (0.75 ± 0.12),overexpression of NF-κB (0.56 ± 0.09) and the ileum injury (1.25 ± 0.05,P ＜ 0.05).These alterations were ameliorated after carbachol administration in LPS-exposed rats.Pretreatment with the α7 nicotinic acetylcholine receptor (α7nAchR) antagonist α-bungarotoxin (α-BGT) blocked the protective action of carbachol.Conclusion Carbachol treatment can protect LPS-induced intestinal barrier dysfunction and the protective effects were associated with activation of cholinergic anti-inflammatory pathway.