OBJECTIVETo investigate the effect of ethyl pyruvate on barrier function of intestinal mucosa in dogs with septic shock.

METHODSTwenty dogs with septic shock induced by lipopolysaccharides(LPS) were randomly divided into two groups. Dogs randomly received placebo (Ringer's solution, control group, n=8) or ethyl pyruvate in lactated Ringer's solution (0.05 g/kg loading dose over 10 mins, thereafter 0.05 g.kg(-1).h(-1) for 12 hours, EP treatment group, n=12). The diamine oxidase(DAO) activity and D-lactate content were detected at the 0, 8 th, 12 th and 24 th hour of septic shock. Animals were sacrificed at the 24 th hour after septic shock and the jejunal tissue was taken for histopathological examination.

RESULTSThe levels of plasma DAO and D-lactate were significantly elevated in both groups after septic shock than those before septic shock. The changes in intestinal parameters of hemoperfusion and permeability in EP treatment group were significantly lowered than those in control group. Inflammation of small intestinal mucosa was more severe in control group than that in EP group, and the pathologic score was significantly lower in EP group(2.33+/-0.25) than that in control group(3.39+/-0.38)(P<0.05).

CONCLUSIONEthyl pyruvate can lessen intestinal permeability and protect intestinal barrier function in dogs with septic shock.

Animals ; Dogs ; Intestinal Mucosa ; drug effects ; pathology ; Intestine, Small ; Male ; Pyruvates ; therapeutic use ; Shock, Septic ; drug therapy ; pathology

No abstract available.
Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; *Capsule Endoscopy ; Female ; Humans ; Intestinal Diseases/*pathology ; Intestine, Small/*drug effects/*pathology ; Male ; Ulcer/*pathology

OBJECTIVETo investigate the dynamic changes of intestinal epithelial stem cells during the injured-repaired progress induced by 5-FU.

METHODSFifty adult C57BL/6J mice were enrolled in this study, 40 of them were intraperitoneally injected with 5-FU (30 mg per kg of body weigh) for five days, and 10 of them intraperitoneally injected with PBS as control. At day 1, 3, 5, 7 after treatment, the mice were killed and middle intestine was taken. Pathology was examined by HE staining. Musashi-1 (msi-1) expression was detected by immunohistochemical technique. The percentage of Rho low staining cells was detected by flow cytometry.

RESULTSAfter treatment with 5-FU, the intestinal mucosa was damaged. The Rho low staining cells were increasing, and at day 1 after treatment, the percentage of Rho low staining cells reached the highest level (P<0.01). The number of cells expressing msi-1 did not change significantly (P>0.05), but the percentage of positive msi-1 cells increased significantly (P<0.01). There was positive correlation between the percentage of Rhodamine 123 low staining cells and positive msi-1 cells in each group (r=0.867, P<0.01).

CONCLUSIONSThe Rho low staining cells may contain rich intestinal epithelial stem cells. The intestinal epithelial stem cells expressing msi-1 can regenerate the damage of intestinal mucosa induced by 5-FU.

Animals ; Cell Line ; Epithelial Cells ; cytology ; drug effects ; Female ; Fluorouracil ; adverse effects ; Intestinal Mucosa ; cytology ; drug effects ; pathology ; Intestine, Small ; cytology ; drug effects ; pathology ; Intestines ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Stem Cells ; drug effects

AIMTo investigate the protective effects of glucagon-like peptide 2(GLP-2) on intestinal ischemia/reperfusion (I/R) injury in mice.

METHODSIntestinal ischemia/reperfusion model in mice were set up and 32 mice of Kunming species were divided randomly into 4 groups (n=8): Sham group, I/R group, I/R + GLP-2 group and I/R + glutamine group. The morphologic changes of intestinal mucosa were observed under LM. The villus height and crypt depth of intestine, the activity of diamine oxidase (DAO) in intestine and bacterial translocation rates of mesenteric lymph nodes (MLN) were detected.

RESULTSCompared with sham operation group, the intestinal villi were sloughed in I/R group with decreased villus height and crypt depth (P < 0.01), the DAO activities were decreased (P < 0.01), and MLN bacterial translocation rates were increased (P < 0.05). While GLP-2 administration improved the villus damage, increased DAO activity (P < 0.01), and decreased MLN bacterial translocation rates (P < 0.05), compared with I/R group.

CONCLUSIONGLP-2 have protective effects on intestinal morphology and barrier function after ischemia/reperfusion injury in mice.

Animals ; Disease Models, Animal ; Glucagon-Like Peptide 2 ; pharmacology ; Intestinal Mucosa ; drug effects ; pathology ; physiopathology ; Intestine, Small ; blood supply ; Male ; Mice ; Mice, Inbred Strains ; Reperfusion Injury ; pathology ; physiopathology

OBJECTIVETo detect the expression of proliferating cell nuclear antigen (PCNA) in severely damaged intestinal mucosa due to high-dose 5-FU exposure.

METHODSThirty-two adult C57BL/6J mice were subjected to daily intraperitoneal high-dose 5-FU injection at 150 mg/kg for 5 consecutive days, and on days 1, 3, and 5, the mice were sacrificed to obtain the small intestinal tissue for HE straining and immunohistochemistry for detecting PCNA expression. Another 8 mice with intraperitoneal PBS injection served as the control group.

RESULTSHigh-dose 5-FU exposure of the mice resulted in severe intestinal mucous damage, with complete destruction of the villi and crypts and significantly increased cells positive for PCNA expression (P<0.01).

CONCLUSIONHigh-dose 5-FU treatment can significantly increase the PCNA index, and the cells expressing PCNA can be closely associated with regeneration of the severely damaged mucosa due to the exposure.

Animals ; Antimetabolites, Antineoplastic ; adverse effects ; Fluorouracil ; adverse effects ; Intestinal Mucosa ; drug effects ; metabolism ; pathology ; Intestine, Small ; drug effects ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Proliferating Cell Nuclear Antigen ; metabolism

OBJECTIVETo study the preventive effects of jinghua weikang capsule (JWC) on nonsteroidal anti-inflammatory drugs (NSAIDs) induced injury to the mucosa of the small intestine.

METHODSThirty-two Wistar rats were randomly divided into four groups, i.e., the blank control group, the model group, the JWC group, and the esomeprazole group. Diclofenac was administered to rats in the model group, the JWC group, and the esomeprazole group at the daily dose of 15 mg/kg. JWC and esomeprazole was respectively given to those in the JWC group, and the esomeprazole group one day ahead. Normal saline was given to rats in the blank control group. Rats were killed 3 days later. The pathological changes of the small intestine were observed by hematoxylin and eosin stain.

RESULTSCompared with the blank control group, the general score for the small intestine (4.63 +/-0.52 vs 0.00 +/-0. 00) and the pathological score (4.00 +/-0.90 vs 0.00 +/-0. 00) obviously increased in the model group, showing statistical difference (P <0.05). Compared with the model group, the general score for the small intestine (1.88 +/-0.99) and the pathological score (2.11 +/-1.11) obviously decreased in the JWG group, showing statistical difference (P <0.05). Compared with the model group, the general score for the small intestine (2.75 +/-1.28) and the pathological score (2. 30 +/-0.94) obviously decreased in the esomeprazole group, showing statistical difference (P <0.05).

CONCLUSIONJWC could prevent NSAIDs induced injury to the mucosa of the small intestine.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Diclofenac ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Esomeprazole ; pharmacology ; therapeutic use ; Intestinal Mucosa ; drug effects ; pathology ; Intestine, Small ; drug effects ; pathology ; Male ; Phytotherapy ; Rats ; Rats, Wistar

OBJECTIVETo study the effect of glutamine on intestinal epithelial apoptosis by examining changes regarding Bcl-2 and Bax mRNA expressions in the small intestine of young rats with endotoxemia and to explore the protective mechanism that glutamine may have.

METHODSA total of 120 18-day-old rats were randomly assigned into Endotoxemia, Glutamine-treated and Control groups (n = 40 each). The endotoxemia model was established by intraperitoneal injection of endotoxin (4 mg/kg of O55B5 Escherichia coli lipopolysaccharide). Rats in the Glutamine-treated group were intraperitoneally injected with N (2)-L-alanyl-L-glutamine (2 g/kg) along with endotoxin. Rats in the Control group were intraperitoneally injected with an equal volume of normal saline. The entire ileum was collected at 2, 4, 6, 24, and 72 hrs after injection. Bcl-2 and Bax mRNA expressions were detected by semi-quantities reverse transcriptase chain reaction.

RESULTSBcl-2 mRNA was not expressed in the Control and the Endotoxemia groups but increased in the Glutamine-treated group at each time point. Bax mRNA expression was weak in the Control group, and significantly increased in the Endotoxemia group at each time point. The Glutamine-treated group showed noticeably reduced Bax mRNA expression at 2 hrs post-injection while other time points were similar to the Control group. The ratio of Bax and Bcl-2 mRNA expression at each time point in the Endotoxemia group was significantly higher than that in the Control group while the Glutamine-treated group demonstrated significantly lower ratio of Bax and Bcl-2 mRNA expression than both.

CONCLUSIONSGlutamine treatment increased Bcl-2 mRNA expression and decreased Bax mRNA expression, as a result, the ratio of Bax and Bcl-2 mRNA expression decreased. The effects of glutamine resulted in a suppression of intestinal epithelial apoptosis and maintained the integrity of the gut barrier structure.

Animals ; Apoptosis ; drug effects ; Endotoxemia ; drug therapy ; pathology ; Female ; Glutamine ; pharmacology ; Intestine, Small ; drug effects ; pathology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; bcl-2-Associated X Protein ; genetics

OBJECTIVETo observe the effects of recombinant human growth hormone (rhGH) on graft structure and recipient protein metabolism in rat small bowel transplantation (SBT) and total parenteral nutrition (TPN) models.

METHODSTwenty recipients of rat allogeneic heterotopic small bowel transplants (SD-->Wistar) were divided into two groups (GH group and control group). Both groups were supported by standard TPN. Acute rejection was suppressed with CsA 10 mg x kg(-1) x d(-1) intramuscularly. All rats in the experimental group received subcutaneous rhGH 1 U x kg(-1) x d(-1) after transplantation. Morphological mucosal indices of transplanted gut and metabolic parameters such as body weight, nitrogen balance, urinary 3-methyl histidine excretion and serum albumin of the recipients were compared between two groups.

RESULTSThe application of rhGH promoted graft recovery significantly compared with standard TPN support alone. On postoperative day 14, all morphological indexes of transplanted gut recovered to the preoperative state. Protein metabolism in the recipient was also significantly improved. rhGH decreased the catabolism of protein, accelerated regaining of positive nitrogen balance and corrected hypoalbuminemia.

CONCLUSIONGH is an effective metabolic intervention in SBT. It may promote the structural repair of the graft and correct the metabolic disturbance. It is useful in improving the outcome of clinical SBT.

Animals ; Body Weight ; drug effects ; Human Growth Hormone ; pharmacology ; Humans ; Intestinal Mucosa ; drug effects ; pathology ; Intestine, Small ; transplantation ; Methylhistidines ; urine ; Nitrogen ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Recombinant Proteins ; pharmacology ; Serum Albumin ; drug effects ; metabolism

BACKGROUND/AIMS: The prevalence of peptic ulcer disease has not decreased mainly due to an increase in the use of NSAIDs. This study was conducted in order to determine whether a chronic NSAID-induced gastric inflammation model could be established by repeated administration of NSAID. METHODS: Indomethacin (10 mg/kg) was administered once per week for six weeks in 8- and 26-week rats and animals were sacrificed every week after administration. Gross ulcer index, histologic damage index, myeloperoxidase (MPO) activity, and mucus (glucosamine) levels were measured. Small bowel damage was also evaluated. RESULTS: Gross gastric damage index showed a peak level at three weeks and then decreased slowly in the 26-week indomethacin group. Gastric mucosal glucosamine level increased in both the 8-week (p=0.038) and 26-week groups (p=0.007). In addition, gastric mucosal MPO level decreased in the 8-week group (p=0.018) but did not show a decrease in the 26-week group. Small bowel damage began to occur at three weeks during the schedule and eight of 36 rats (22.2%) died due to perforation or peritonitis of the small bowel in the 8- and 26-week indomethacin groups, respectively. CONCLUSIONS: Due to gastric adaptation and small bowel damage, repeated administration of NSAID to experimental animals may not be an adequate method for establishment of the chronic gastric inflammation model.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*toxicity ; Disease Models, Animal ; Gastric Mucosa/*drug effects/enzymology/pathology ; Glucosamine/metabolism ; Indomethacin/*toxicity ; Intestine, Small/*drug effects/pathology ; Male ; Peroxidase/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors

BACKGROUND/AIMS: The prevalence of peptic ulcer disease has not decreased mainly due to an increase in the use of NSAIDs. This study was conducted in order to determine whether a chronic NSAID-induced gastric inflammation model could be established by repeated administration of NSAID. METHODS: Indomethacin (10 mg/kg) was administered once per week for six weeks in 8- and 26-week rats and animals were sacrificed every week after administration. Gross ulcer index, histologic damage index, myeloperoxidase (MPO) activity, and mucus (glucosamine) levels were measured. Small bowel damage was also evaluated. RESULTS: Gross gastric damage index showed a peak level at three weeks and then decreased slowly in the 26-week indomethacin group. Gastric mucosal glucosamine level increased in both the 8-week (p=0.038) and 26-week groups (p=0.007). In addition, gastric mucosal MPO level decreased in the 8-week group (p=0.018) but did not show a decrease in the 26-week group. Small bowel damage began to occur at three weeks during the schedule and eight of 36 rats (22.2%) died due to perforation or peritonitis of the small bowel in the 8- and 26-week indomethacin groups, respectively. CONCLUSIONS: Due to gastric adaptation and small bowel damage, repeated administration of NSAID to experimental animals may not be an adequate method for establishment of the chronic gastric inflammation model.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*toxicity ; Disease Models, Animal ; Gastric Mucosa/*drug effects/enzymology/pathology ; Glucosamine/metabolism ; Indomethacin/*toxicity ; Intestine, Small/*drug effects/pathology ; Male ; Peroxidase/metabolism ; Rats ; Rats, Sprague-Dawley ; Time Factors