| ObjectiveThe study aimed at exploring the protection method of intestinal mucosa barrier.Intestinal mucosa barrier is the critical interface between the internal and externalenvironments; however, it can be destroyed by many stress factors including thechemotherapy drugs. The chemotherapy drugs can kill tumor cells; meanwhile they alsoinjure the normal intestinal mucosa epithelial cells, leading to intestinal mucosal atrophy,intestinal permeability increasing, and intestinal immune dysfunction and so on. The injuryof intestinal mucosal barrier results in nausea, vomiting, diarrhea, mucosal necrosis，lossblood in the stool and systemic adverse reactions, and even exacerbating the condition orlife-threatening. Therefore, protection the structural integrity and function of intestinalmucosal barrier during chemotherapy is an important issue for prevention of chemotherapyside effects.Glucosamine is a glucose with an amino group at position2, whereas,N-Acetyl-D-glucosamine (GlcNAc) is a glucosamine that is acetylated on the amino group,with low molecular weight and high solubility in water. Previous studies found that,GlcNAc possesses anti-oxidant and immune-modulating effect, and it can effectivelyimprove the intestinal mucosa of local ecological environment, enhance epithelial cellactivity and cure the diarrhea-predominant irritable bowel syndrome effectively. So wespeculated that GlcNAc would have a protective effect for intestinal mucosal injury inducedby chemotherapy. Therefore, this study was designed to investigate the effects and itsmechanism of GlcNAc on intestinal mucosal barrier injury induced by5-FU, and thus lay abasis for the study of protection of intestinal mucosa barrier against chemotherapy drugs.Materials and Methods1．Fifty Sprague-Dawly rats were randomly divided into five groups, i.e. blank control,5-FU model, glutamine, glucosamine and GlcNAc groups; and administrated with normal saline,5-FU, glutamine glucosamine and GlcNAc, respectively.2．The body weights of all animals were measured everyday during experiment period.3．The pathological change of intestinal mucosa was assayed by histological methodafter hematoxylin-eosin staining. The ultra-structure of intestinal mucosa was observed bytransmission electron microscopy.4． Plasma level of D-lactate was detected with spectrophotometer, while theconcentration of DAO in plasma was measured by ELISA.5．The protein expression levels of O-GlcNAc modified proteins in intestinal mucosawere determined by Western blotting.Results1． Compared with the rats before test, body weight of rats in normal control，Gln andGlcNAc group raised normally, however, that of5-FU model and GlcN group droppeddown. The anatomical observations showed that there were no significant change inintestines of rats from normal control and GlcNAc group, whereas, the flatulence, bowelmucosal hyperemia and diarhea existed with different extent.2． Histological observation showed that the structure of intestinal wall in normalcontrol group were clear and complete with the slender, developed villus and arrangedregularly; there were minor injury in GlcNAc group, and obvious injury in5-FU modelgroup.3．Transmission electron microscope indicated that the intestinal mucosa epitheliumcellular junction were abnormal in rats from5-FU model group, on the other hands, thatof rats from GlcNAc group were normal and similar to that of normal control group4. D-lactic acid content in serum of rats from GlcNAc group fell significantly than thatof5-FU model and GlcN group (p <0.01) by31.5%and33.7%respectively; whereas, therewere no statistically significant between GlcN group and5-FU model group (p>0.05).5. DAO content in serum of rats from Gln and GlcNAc group fell significantly thanthat of5-FU model and GlcN group (p <0.01); whereas, there were no statisticallysignificant between GlcN group and5-FU model group (p>0.05).6. The expression levels of O-GlcNAc modified proteins of rats from5-FU model andGlcN group fell significantly than that of normal control group (p <0.01); however, That ofGln and GlcNAc group raised significantly than that of5-FU model and GlcN group (p < 0.01); whereas, there were no statistically significant between GlcN group and5-FU modelgroup (p>0.05).Conclusions1．GlcNAc can efficiently attenuate intestinal mucosa injury in chemotherapy rats,down regulate the intestinal mucosa permeability, and protect the function of intestinalmucosa barrier.2．GlcNAc can improve the protein expression levels of O-GlcNAc modified proteinsin Intestinal mucosa. This may be contributing to the protection effect of GlcNAc on thefunction of intestinal mucosa barrier. |
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