Department of Anesthesia, Critical Care Medicine & Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People's Republic of China.
Biochem Biophys Res Commun. 2012 Nov 16;428(2):321-6. doi: 10.1016/j.bbrc.2012.10.056. Epub 2012 Oct 23.
Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-κβ) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the α7 nicotinic acetylcholine receptor (α7nAchR) antagonist α-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-κβ and MLCK pathways in an α7nAchR-dependent manner.
卡巴胆碱是一种拟胆碱能激动剂，可在创伤或烧伤后保护肠道。本研究旨在确定卡巴胆碱的有益作用及其改善脂多糖（LPS）诱导的肠道屏障破坏的机制。大鼠腹腔内注射 10mg/kg LPS。结果表明，卡巴胆碱给药可降低肠道屏障通透性，防止紧密连接（TJ）的超微结构破坏，部分逆转闭合蛋白-1 和紧密连接蛋白-2 蛋白的重新分布，并抑制 LPS 暴露大鼠肠上皮细胞中核因子-κβ（NF-κβ）和肌球蛋白轻链激酶（MLCK）的激活。α7 烟碱型乙酰胆碱受体（α7nAchR）拮抗剂α-银环蛇毒素预处理可阻断卡巴胆碱的保护作用。这些结果表明，卡巴胆碱治疗可保护 LPS 诱导的肠道屏障功能障碍。卡巴胆碱通过抑制 NF-κβ 和 MLCK 通路发挥其有益作用，这种作用依赖于 α7nAchR。
