The study was based on the toxic characteristics of the compatibility between "Zaojisuiyuan" and Gancao, with intestinal tract and intestinal bacteria as subject. From the angle of intestinal barrier function, motor function, steady state of intestinal flora and metabolism genes, the toxic and side effects of the compatibility between Qianjinzi and Gancao with similar properties, bases and chemical composition and types were further explored. The results showed that the combined application of Qianjinzi and Gancao enhanced intestinal mucosa damage, and led to abnormal changes in intestinal bacteria structure and metabolic function. It improved the degradation functions of mucus and aromatic amino acids on intestinal bacteria, which may increase the risk of disease and derived from intestinal urotoxin and other toxic substances. This study considered intestinal bacteria as an important target to study the interactions of traditional Chinese medicine. The "drug-intestinal bacteria-metabolism-toxicity" was applied in the experiment. Meanwhile, it provides ideas for exploring incompatible mechanism of traditional Chinese medicines.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Gastrointestinal Microbiome ; drug effects ; Glycyrrhiza uralensis ; chemistry ; Intestinal Mucosa ; drug effects ; pathology ; Medicine, Chinese Traditional

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

OBJECTIVETo observe the effect of Qihuang Decoction (QHD) on epithelial cell apoptosis of ischemia-reperfusion (I/R) injured intestinal mucosa in rat.

METHODSThe I/R injured intestinal mucosa rat model was established by clamping superior mesenteric artery (SMA) for 45 min and reperfusing for 60 min. The pathomorphological Changes and epithelial cell apoptosis in the injured intestinal mucosa were observed and compared among groups: the sham-operated group (A), the model group (B), the glutamine treated group (C) and the QHD treated group (D).

RESULTSpathomorphological examination showed that in group A, the intestinal villus was intact; in group B, the intestinal subepithelial space were dilated, and showed evident cleavage between the epithelial top and the lamina propria with bare capillaries, bleeding and ulceration; in group C and D, the above-mentioned pathomorphological changes were alleviated to some extents, appeared only in part of the villa, and the alleviation was more significant in group D than in group C. Chiu's scoring showed that the lowest score (zero) presented in group A and the highest presented in group B; scores in group C and D was significantly lower than that in group B (P < 0.05), but showed insignificant difference between the two groups (P > 0.05). Epithelial cell apoptosis detection showed that the least apoptosis rate presented in group A, and the highest in the group B; while in the group C, it lied between group A and B (all P < 0.05), and showed no statistical significance to group D (P > 0.05), though appeared a lowering trend.

CONCLUSIONQHD could reduce the I/R injured intestinal epithelial mucosa, and its protective mechanism may be related to the inhibition on apoptosis of intestinal mucosal epithelial cells.

Animals ; Apoptosis ; drug effects ; Astragalus Plant ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; drug effects ; Intestinal Mucosa ; blood supply ; drug effects ; pathology ; Male ; Rats ; Rats, Wistar ; Reperfusion Injury ; 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

OBJECTIVE: To investigate the protective effects of shen-mai injection on intestinal barrier function in the early stage of 30% 3° scald, and to provide experimental basis for the prevention and control of enterogenic infection. METHODS: A total of 60 Wistar rats were randomly divided into 6 groups: normal control group (without treatment), model control group (with 30% total body surface area (TBSA) fully thickness burn on the back), hexadecadrol (5 mg/kg) group, Shenmai injection (5, 10, 15 mg/kg) groups, with 10 rats in each group. After burned by scald apparatus, rats in each group were treated with drugs immediately by intraperitoneal injection once a day. At 72 hours after burned, the levels of plasma endotoxin, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interleukins-6(IL-6) in all rats were detected and the mesenteric lymph nodes, liver and spleen were homogenized to culture for bacteria. The change of secretory immunoglobulin A (sIgA) in intestinal mucosa was measured. RESULTS: Compared with normal control group, bacterial translocation quantity in mesenteric lymph nodes(MLN), liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in model control group were increased significantly (P＜0.01); compared with model control group, bacterial translocation quantity in MLN, liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in hexadecadrol (5 mg/kg) group and shen-mai injection (5, 10, 15 mg/kg) groups were decreased significantly (P＜0.05 or P＜0.01). CONCLUSION Shen-mai injection can alleviate intestinal mucosa injury caused by severe scald, and the effects are similar with those of dexamethasone, and the effect is better in the high-dose group.
Animals ; Bacterial Translocation ; drug effects ; Burns ; complications ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Intestinal Mucosa ; drug effects ; pathology ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effects of ulinastatin on gut mucosal apoptosis and bacterium translocation in a rat model of sepsis.

METHODSFifty rats were randomly assigned into 4 groups, namely the control (n=5, no operation or drugs), ulinastatin pretreatment (n=15, treated with 25,000 U/kg ulinastatin 2 h before operation), ulinastatin treatment (n=15, treated with 25,000 U/kg ulinastatin 2 h after operation) and sepsis model (n=15, without drug treatment) groups. The rats in the later 3 groups were subjected to cecal ligation and puncture (CLP). At 3, 6 and 12 h after CLP, the rats were sacrificed and the ileum was removed to examine the pathology and apoptosis of the mucosa. The DNA of Bacillus coli in the whole blood was detected using PCR.

RESULTSSepsis caused of epithelial cell loss in the ileal villi, ulceration and blebbing of the lamina propria. Ulinastatin treatment administered before and after the operation both significantly alleviated these morphological anomalies. The sepsis rats showed significantly increased intestinal mucosal apoptotic index as compared with the other 3 groups (P<0.05). Ulinastatin pretreatment, in comparison ulinastatin treatment 12 h after CLP, significantly increased the intestinal mucosal apoptotic index (P<0.05). Bacillus coli DNA was positive in sepsis and postoperative ulinastatin treatment groups but negative in the control and pretreated groups.

CONCLUSIONIncreased intestinal musocal apoptosis and gut bacterial translocation occur in rats following sepsis, and ulinastatin can effectively decrease intestinal mucosal apoptosis and inhibit bacterial translocation.

Animals ; Apoptosis ; drug effects ; Bacterial Translocation ; drug effects ; Female ; Glycoproteins ; pharmacology ; therapeutic use ; Ileum ; drug effects ; microbiology ; pathology ; Intestinal Mucosa ; drug effects ; microbiology ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sepsis ; drug therapy ; Trypsin Inhibitors ; pharmacology ; therapeutic use

Colonic necrosis is known as a rare complication following the administration of Kayexalate (sodium polystryrene sulfonate) in sorbitol. We report a rare case of colonic mucosal necrosis following Kalimate (calcium polystryrene sulfonate), an analogue of Kayexalate without sorbitol in a 34-yr-old man. He had a history of hypertension and uremia. During the management of intracranial hemorrhage, hyperkalemia developed. Kalimate was administered orally and as an enema suspended in 20% dextrose water to treat hyperkalemia. Two days after administration of Kalimate enema, he had profuse hematochezia, and a sigmoidoscopy showed diffuse colonic mucosal necrosis in the rectum and sigmoid colon. Microscopic examination of random colonic biopsies by two consecutive sigmoidoscopies revealed angulated crystals with a characteristic crystalline mosaic pattern on the ulcerated mucosa, which were consistent with Kayexalate crystals. Hematochezia subsided with conservative treatment after a discontinuance of Kalimate administration.
Adult ; Colon/*pathology ; Gastrointestinal Hemorrhage/etiology ; Humans ; Hyperkalemia/drug therapy ; Intestinal Mucosa/*pathology ; Male ; Necrosis/*chemically induced/complications/pathology ; Polystyrenes/*adverse effects/therapeutic use ; Uremia/*physiopathology

OBJECTIVETo explore the influence of recombinant human growth hormone (rhGH) on the apoptosis and intestinal mucosal structure in severely scalded rats.

METHODSThirty male Wistar rats were randomly divided into three groups, i.e. control, scalding and rhGH groups. The rats in scalding and rhGH groups were inflicted with 25% TBSA III degree scalding on the back and immediately followed by intraperitoneal injection of dexamethasone (80 mg/kg). The scalded rats were administered with normal saline and rhGH (1.33 IU.kg(-1).d(-1)) since 2 postburn hours (PBHs), respectively in the last two groups. The changes of the apoptosis rate, the intestinal mucosal proliferative index (PI) and epithelial ultrastructure and the intestinal mucosal pathomorphology of the distal end of ileal mucosal tissue were observed on 30 and 96 PBHs.

RESULTSThe intestinal mucosa morphology and epithelia in scalding group were severely injured but were significantly ameliorated by rhGH to near those in control group. The PI in rhGH and scalding groups at 30 PBHs was evidently higher that that in control group (P < 0.05 - 0.01). But the PI exhibited no obvious difference between scalding and rhGH groups. While the PI in rhGH group at 96 PBHs was obviously higher than that in both scalding and control groups (P < 0.01). The intestinal mucosal epithelial apoptotic rate in scalding group was significantly higher than that in control group (P < 0.01), while that in rhGH group was evidently lower than that in scalding and control groups (P < 0.05 - 0.01).

CONCLUSIONrhGH could promote postburn intestinal mucosa epithelial proliferation in slow - action manner and inhibit intestinal mucosal epithelial apoptosis with rapid and obvious effects. As a result, the intestinal mucosal epithelial injury could be ameliorated by rhGH by means of its inhibiting roles and the normal morphological structure of intestinal mucosa was maintained ad hoc.

Animals ; Apoptosis ; Burns ; pathology ; Human Growth Hormone ; genetics ; pharmacology ; Intestinal Mucosa ; drug effects ; pathology ; Male ; Rats ; Rats, Wistar ; Recombinant Proteins ; pharmacology

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

OBJECTIVEThis study aimed to investigate the roles of platelet activating factor (PAF) receptor antagonist in damage to intestinal mucin-2 (MUC2) during endotoxemia on young rats.

METHODSEighteen-day-old Wistar rats were randomized to be treated with lipopolysaccharide (LPS) (5 mg/kg), LPS plus PAF receptor antagonist and normal saline injection (control). PAF receptor antagonist BN52021 5 mg/kg was administered 30 minutes before or after LPS injection (pretreatment group or treatment group). The ileum specimens (n = 8) were harvested at 1.5, 3, 6, 24, 48 and 72 hours after LPS injection. Transmission electron microscopy was used for morphologic evaluation. Immunohistochemistry was used to determine MUC2 in intestinal mucosa.

RESULTSMicrovilli and tight junctions were intact in the control group. Enlargement of tight junctions were seen in the LPS group and microvilli were thin, rare or disrupted, shed. The rough endoplasmic reticulum, mitochondria, and glycogen particles were injured. The changes of the pretreatment and treatment group were slightly milder than that in the LPS group. Ileum of a control rat in which a thin layer of mucus covering the epithelial surface and mucin-containing goblet cells appeared very distended. The experiment group showed a decrease or irregularly distributed membranous mucus expression. The MUC2 content of absorbance significantly decreased in the LPS challenged group compared with that in the control group (P < 0.01), and reached a nadir at 6 hours (0.1841 +/- 0.0047) vs. the control group (0.2091 +/- 0.0060) (P < 0.01). The tendency of the level of MUC2 in the pretreatment and treatment group was the same as that of the LPS group, and the level of MUC2 in the pretreatment and treatment group was higher than that in the LPS group at each time point. ANOVA analysis showed that the inter-group and intra-group difference had statistical significance (P < 0.05).

CONCLUSIONSPAF may play some roles in the injury of intestinal mucus barrier function during endotoxemia. Preventive and remedial use of PAF receptor antagonist BN52021 may relieve intestinal injury.

Animals ; Endotoxemia ; metabolism ; pathology ; Intestinal Mucosa ; drug effects ; metabolism ; pathology ; Mucin-2 ; metabolism ; Platelet Membrane Glycoproteins ; antagonists & inhibitors ; Rats ; Rats, Wistar ; Receptors, G-Protein-Coupled ; antagonists & inhibitors