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Glutamine depletion induces murine neonatal melena with increased apoptosis of the intestinal epithelium

World Journal of Gastroenterology 2011年第6期17卷 717-726页

作者： Takayuki Motoki Yoshio Naomoto Junji Hoshiba Yasuhiro Shirakawa Tomoki Yamatsuji Junji Matsuoka Munenori Takaoka Yasuko Tomono Yasuhiro Fujiwara Hiroshi Tsuchita Mehmet Gunduz Hitoshi Nagatsuka Noriaki Tanaka Toshiyoshi Fujiwara Department of Gastroenterological Surgery Transplantand Surgical OncologyGraduate School of MedicineDentistryand Pharmaceutical SciencesOkayama University Department of General Surgery Kawasaki Medical School Kawasaki Hospital Division of Molecular and Cell Biology Shigei Medical Research Institute Department of Animal Resources Advanced Science Research CenterOkayama University Food Technology Research Institute Meiji Dairies Corporation Department of Oral Pathology and Medicine Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama University

AIM:To investigate the possible biological outcome and effect of glutamine depletion in neonatal mice and rodent intestinal epithelial ***:We developed three kinds of artificial milk with different amounts of glutamine;Complete amino acid milk (CAM),which is based on maternal mouse milk,glutamine-depleted milk (GDM),and glutaminerich milk (GRM).GRM contains three-fold more glutamine than ***-seven newborn mice were divided into three groups and were fed with either of CAM,GDM,or GRM via a recently improved nipple-bottle system for seven *** the feeding period,the mice were subjected to macroscopic and microscopic observations by immunohistochemistry for 5-bromo-2'deoxyuridine (BrdU) and Ki-67 as markers of cell proliferation,and for cleaved-caspase-3 as a marker of ***,IEC6 rat intestinal epithelial cells were cultured in different concentrations of glutamine and were subject to a 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)2H-5-tetrazolio]-1,3-benzene disulfonate cell proliferation assay,flow cytometry,and western blotting to examine the biological effect of glutamine on cell growth and ***:During the feeding period,we found colonic hemorrhage in six of 28 GDM-fed mice (21.4%),but not in the GRM-fed mice,with no differences in body weight gain between each *** examination showed destruction of microvilli and the disappearance of glycocalyx of the intestinal wall in the colon epithelial tissues taken from GDM-fed *** of GDM reduced BrdU incorporation (the average percentage of BrdU-positive staining;GRM:13.8%,CAM:10.7%,GDM:1.14%,GRM vs GDM:P < 0.001,CAM vs GDM:P < 0.001) and Ki-67 labeling index (the average percentage of Ki67-positive staining;GRM:24.5%,CAM:22.4% GDM:19.4%,GRM vs GDM:P=0.001,CAM vs GDM:P =0.049),suggesting that glutamine depletion inhibited cell proliferation of intestinal epithelial *** deprivation further caused the deformation of the nuclear membrane and the plasma m

关键词： Glutamine Newborn mice artificial milk Melena Intestinal epithelial cells Apoptosis

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