甘油可能通过水通道蛋白3减轻脓毒症小鼠肠黏膜屏障损伤

目的探讨甘油对脓毒症小鼠肠黏膜屏障功能的保护作用。方法将小鼠随机分为4组:假手术组、假手术+口服甘油组、脓毒症模型组小鼠(n=30),用盲肠结扎穿孔术(CLP)建立脓毒症模型,其中24只分别于建模后0、6、12和24 h处死,每个时点6只,作为时间依赖实验(时间依赖)]、脓毒症+口服甘油组。除时间依赖组,4组小鼠建模后24 h处死,收集血液和肠黏膜组织标本。用HE染色观察小肠黏膜病理损伤;ELISA测定二胺氧化酶(DAO)和肠型脂肪酸结合蛋白(FABP2)血浆浓度,检测肠黏膜通透性;免疫组化、RT-qPCR、Western blot检测肠黏膜水通道蛋白3(AQP3)表达。结果脓毒症诱导肠黏膜形态损伤,形态无序破坏,Chiu's评分呈时间依赖性升高(P<0.05);血浆DAO和FABP2浓度显著升高(P<0.05);AQP3表达随肠黏膜损伤加重表达明显下调(P<0.05)。口服甘油治疗部分改善脓毒症诱导的肠黏膜损伤,表现为肠黏膜形态结构改善、Chiu's评分降低以及血浆DAO和FABP2浓度降低。结论口服甘油治疗可能通过AQP3减轻脓毒症小鼠肠黏膜屏障损伤。其具体机制有待于进一步研究。

Glycerol may reduce intestinal mucosal barrier damage in sepsis mice through aquaporin 3

Objective To explore the protective effect of oral glycerol on sepsis induced intestinal mucosal barrier function.Methods Mice were randomly divided to four groups:sham operation(n=6);sham operation with oral glycerol(n=6);Mouse sepsis model(n=30)was established using cecal ligation and puncture(CLP),of which 24 mice were executed at 0,6,12 and 24 h after CLP respectively(6 mice at each time point)as a time-dependent group,and sepsis with oral glycerol group(n=6).Besides the time-dependent group,four groups of mice were executed at 24 h after modeling.Blood and intestinal mucosal tissue samples were collected.HE staining was used to detect pathological damage of intestinal mucosa.The plasma diamine oxidase(DAO)concentration and intestinal-type fatty acid-binding protein 2(FABP2)concentration were measured by ELISA to assess intestinal mucosal permeability.Immunohistochemistry,real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blot were used to detect the expression of AQP3 in intestinal mucosa.Results Sepsis induced morphological damage of intestinal mucosa,and the Chiu's score increased in a time-dependent manner(P<0.05).The concentrations of DAO and FABP2 in plasma were significantly increased(P<0.05),and the expression of AQP3 significantly down-regulated with the aggravation of injury(P<0.05).The administration of oral glycerol partially improved the sepsis-induced injury of the intestinal mucosa,as shown by partial recovery of the morphological structure,with decreased Chiu's score,decreased plasma concentrations of DAO and FABP2(sepsis vs sepsis+glycerol,P<0.05).Conclusions Oral treatment with glycerol may alleviate intestinal mucosal barrier damage in sepsis mice through aquaporin-3.The specific mechanism needs to be further studied.