短链脂肪酸对新生鼠肠黏膜屏障的作用研究

Effect of short chain fatty acid on intestinal barrier functions in neonatal rat

目的通过在体外检测生理浓度短链脂肪酸（SCFAs）作用下的新生鼠肠黏膜，探索SCFAs对于维持正常肠黏膜屏障的作用。方法取SD大鼠近端结肠组织，分断奶前组（n=8，日龄13-17d），断奶后组（n=6，日龄24-31d）。在尤斯灌流系统内37℃水浴（95％O2，5％CO2），黏膜侧水槽分别加入含乙酸Kreb液（乙酸浓度分别为0、20、80mmol／L，pH6．0）或者是含丁酸Kreb液（丁酸浓度分别为0、5、20mmol／L，pH6．0）。实时记录跨上皮电阻（TER），并检测不同时间段（0、30、60、90、120mins）黏膜对侧FITC-dextran浓度。结果在未加入任何SCFAs情况下，90min后断奶后组与断奶前组相比，结肠黏膜透过率明显降低，而TER明显升高（P〈0．01）。从120min的实时记录来看，在黏膜侧加入80mmol／L乙酸后，两组的TER均出现显著上升（P〈0．05），但在丁酸实验中未发现如此明显效应（P〉0．05）。结论断奶前的新生鼠肠黏膜屏障尚未完全成熟；在新生鼠结肠离体模型中，生理浓度乙酸在维持正常肠黏膜屏障功能比丁酸更为有效。

Objective We hypothesized that short chain fatty acids（SCFAs） exposing to muco- sal lumen play an important role in the maintenance of the intestinal barrier. So the aim of this study was to examine the ex vivo effects of short chain fatty acids （SCFAs） with physiological concentrations on intestinal barrier functions in neonatal rat. Methods The proximal colonic tissue derived from SD rat was harvested,and they were divided into pre-weaning group （n = 8, ranging from 13 to 17 days） and post-weaning group （n = 6, ranging from 24 to 31 days）. The intestinal mucosa was mounted in Ussing chambers （95% 02 and 5% CO2 ） containing warm water bath （37 ℃）. After equilibration for 15-20 minutes,the mucosal tissue was exposed to the acetate-containing Krebs solutions （0,20 or 80 mmol/L concentration, pH 6. 0） or the butyrate-containing Krebs solutions （0,5 or 20 mmol/L con- centration, pH 6. 0）. Transepithelial electrical resistance （TER） and permeability calculated by meas- uring transepitheliat FITC-dextran concentration at various time points （0,30,60,90 and 120 minutes） were recorded. Results The overall colonic mucosa permeability was significantly lower in the post- weaning rats than those in pre-weaning rats （P〈0. 01） ,but TER detection. At the time course of 120- minute, a TER increasing was found significantly once exposing to 80 mmol/L acetate-containing Krebs solutions in both groups（P〈0. 05）. However,such phenomenon was not seen in butyrate-con- taining Krebs solutions（P〉0. 05）. Conclusions Intestinal barrier function is still immature in pre- weaning rats. Regarding to the neonatal rat mucosa ex vivo model, acetate plays more important role in the maintenance of intestinal barrier function than butyrate.