Factors influencing intercellular spaces in the rat esophageal epithelium.

AIM: To evaluate the effect of acute stress, hydrochloric acid, ethanol, aspirin, and prednisolone on the intercellular spaces of the esophageal epithelium. METHODS: Part I, male Sprague-Dawley rats were randomly divided into eight groups and treated with the damaging or control factors. The esophagus of each rat was macroscopically inspected. Histological changes in mucosal biopsies were examined by light microscopy, and the widths of intercellular spaces were determined by transmission electron microscopy (TEM). Part II, in part I, we found that acute stress and aspirin induced dilated intercellular spaces (DIS) of the esophageal epithelium. Therefore, the effect of acid suppression pretreatment with esomeprazole on esophageal epithelial DIS induced by water immersion and restraint stress (WRS) and aspirin was further investigated to determine the association of DIS with acid reflux. After administration of 0.9% sodium chloride solution or esomeprazole solution orally for five days, rats underwent WRS or intragastric administration of aspirin solution. Esophageal epithelial intercellular spaces were investigated by TEM. RESULTS: (1) The five damaging factors produced no lesions or inflammation in esophageal mucosa of rats under either gross or routine histological inspections. Esophageal epithelial intercellular space diameters in stress and aspirin groups were significantly greater, nearly three or two-fold respectively, than those in their corresponding control groups (stress model: 0.38 + or - 0.05 microm vs 0.13 + or - 0.02 microm, P < 0.01; aspirin model: 0.32 + or - 0.12 microm vs 0.19 + or - 0.05 microm, P < 0.01). Neither intragastric administration of hydrochloric acid or ethanol, nor hypodermic injection of prednisolone produced DIS compared with their corresponding control groups (hydrochloric acid model: 0.24 + or - 0.03 microm vs 0.19 + or - 0.05 microm, P > 0.05; ethanol model: 0.25 + or - 0.10 microm vs 0.19 + or - 0.05 microm, P > 0.05; prednisolone model: 0.20 + or - 0.03 microm vs 0.14 + or - 0.03 microm, P > 0.05); and (2) No significant difference in the intercellular space diameters was observed between the group pretreated with esomeprazole and the control group, in both the stress and aspirin models (stress model: 0.35 + or - 0.05 microm vs 0.37 + or - 0.05 microm, P > 0.05; aspirin model: 0.24 + or - 0.02 microm vs 0.27 + or - 0.03 microm, P > 0.05). CONCLUSION: Acute stress and aspirin can induce DIS of the esophageal epithelium in rats, and it is not correlated with acid reflux.

[Mechanism of exacerbation of colonic damage in experimental colitis treated with celecoxib].

OBJECTIVE: To assess the mechanism of exacerbation of colonic damage in rat colitis model induced by trinitrobenzene sulfonic acid (TNBS) treated with celecoxib (a selective COX-2 inhibitor). METHODS: The rats were randomized into four groups. Group 1 and Group 2 were study groups. Group 3 and Group 4 were control groups. Colitis was induced by intracolonic administration of TNBS (25 g/L) in a vehicle of 50% ethanol (0.25 mL) of study groups. The rats of study groups were treated orally, beginning 3 h before induction of colitis and continuing twice per day thereafter for up to 7 d, with celecoxib (1.25 mg/kg, Group 1) and distilled water (1 mL/0.3 kg, Group 2) respectively. In control experiments, the rats of Group 4 were treated orally with celecoxib (1.25 mg/kg) twice per day for up to 7 d. Group 3 rats were healthy control rats. All the rats that survived until the end of the experiment (d 7) were killed and the severity of colonic inflammation was assessed. The COX-2 protein expression in colon tissues was examined by immunohistochemistry. RESULTS: The colonic damage of Group 1 was exacerbated as compared with Group 2. The inflammatory index of colon tissues of Group 1 (8.5+/-2.5) was significantly reduced, as compared with Group 2 (13.5+/-1.9, P<0.05). The levels of COX-2 protein expression was decreased significantly in Group 1 (3.7 x 10(-2)+/-9.5 x 10(-3)) as compared with Group 2 (11.4 x 10(-2)+/-3.8 x 10(-2), P<0.05). The positive rate of COX-2 expression in neural cells of the myenteric plexus in Group 1 (30%) was decreased as compared with Group 2 (90%, P<0.05). No difference was found in the inflammatory index, the levels of COX-2 protein expression and the positive rate of COX-2 expression in neural cells of the myenteric plexus of Group 3 and Group 4. CONCLUSION: Selective COX-2 inhibitor-celecoxib could decrease the expression of COX-2 in intestinal tissue, attenuate the inflammatory index of colon tissues of experimental colitis induced by TNBS. But the application of celecoxib resulted in exacerbation of colonic damage. These adverse events are probably relevant to the suppression of COX-2 expression in the neural cells of the myenteric plexus, leading to decrease of intestinal contractivity and peristalsis, enteroparalysis, megacolon and death of the rat.

[Distribution of Helicobacter pylori in stomach before and after the administration of Lansoprazole].

OBJECTIVE: To investigate the effect of the acid inhibitor-Lansoprazole on the distribution of Helicobacter pylori (H.pylori) in stomach. METHODS: Biopsy specimens were taken from the duodenal ulcer patients who underwent gastroscopy before and after the treatment of Lansoprazole. The biopsy specimens were taken from the lesser curvature of the antrum and the greater curvature of the corpus respectively. H&E and Warthin-Starry staining were used for detecting the changing of active gastritis and the positive rate of H.pylori. RESULTS: (1)The positive rates of H.pylori before treatment, 4 weeks after treatment and 3 months after treatment, in the lesser curvature of the antrum were 93.02%, 58.14%, and 86.05%, respectively. The positive rate and density of H.pylori 4 weeks after treatment were greatly decreased compared with those before treatment (P<0.001) and also lower than those 3 months after treatment (P<0.05). (2) The positive rate of H.pylori before treatment, 4 weeks after treatment and 3 months after treatment in greater curvature had differences without statistical significance. However, the density of H.pylori 4 weeks after treatment was increased compared with that before treatment. CONCLUSION: Lansoprazole can change the colonization site of H.pylori in the stomach, decrease the positive rate and the density of H.pylori in lesser curvature of the antrum, but increase the density of H.pylori in the greater curvature of the corpus. This effect is most obvious in one month after treatment. Active gastritis is related to H.pylori.

Effects and mechanism of the selective COX-2 inhibitor, celecoxib, on rat colitis induced by trinitrobenzene sulfonic acid.

OBJECTIVE: To investigate the action of celecoxib (a selective COX-2 inhibitor) in a rat model of colitis induced by trinitrobenzene sulfonic acid (TNBS). METHODS: Rats were randomized into four groups. Colitis was induced in groups 1 and 2 by intracolonic administration of TNBS (25 mg/mL) in 50% ethanol (0.25 mL). The rats in group 1 received oral celecoxib (1.25 mg/kg) and those in group 2 received distilled water (1 mL/0.3 kg), beginning 3 h before induction of colitis and continuing twice daily thereafter for up to 7 days. The rats in group 4 received oral celecoxib (1.25 mg/kg) twice daily for 7 days and those in group 3 were healthy controls. All rats that survived 7 days were killed and both the severity of colonic mucosal damage and the prostaglandin E2 (PGE2) concentrations of the colonic mucosa were assessed. RESULTS: The colonic mucosal damage scores for groups 1 and 2 were 11.15 +/- 3.30 and 8.50 +/- 2.82, respectively, both of which were significantly higher than the score for the healthy controls (0.62 +/- 0.09; P < 0.01, P < 0.01). The score of group 1 was significantly higher than that of group 2 (P < 0.05). No difference was found between the scores of groups 3 and 4. The mucosal concentrations of PGE2 in groups 1 and 2 were 12.00 +/- 4.33 pg/microg and 17.20 +/- 9.62 pg/microg, respectively, both of which were significantly higher than the concentration in the healthy controls (6.02 +/- 3.39 pg/microg; P < 0.05, both). The PGE2 concentration of group 1 was decreased significantly compared with that of group 2 (P < 0.05). No difference was found between groups 3 and 4. CONCLUSION: The results suggest that treatment with celecoxib exacerbates inflammation-associated colonic injury in experimental colitis induced by TNBS. This preliminary study shows that the mechanism is related to suppression by the COX-2 inhibitor of the PG derived from COX-2, but further study is needed to identify if there are other related mechanisms.

[The roles of dopamine 4 receptor in MPTP-induced gastrointestinal mucosal injury in rats].

OBJECTIVE: Using the dopamine 4 receptor (D(4)) agonist quinpirole (Q.) and antagonist clozapine (C.) to investigate the role of D(4) in MPTP induced gastrointestinal injury in rat. METHODS: SD rats were randomly divided into 8 groups (n = 5 approximately 9 each group): NS as control; Q. 0.5 mg/kg; Q. 1 mg/kg; C. 10 mg/kg; Q. 0.5 mg/kg + MPTP; Q. 1 mg/kg + MPTP; and MPTP l mg/100 g. After treated with the different chemicals, the gastric and duodenal mucosa lesion index (LI) was recorded. Gastric and duodenal mucosa was collected to assay NO and iNOS by spectrophotometer. RESULTS: (1) MPTP peritoneal injection induced significant gastro-duodenal mucosa injury; both gastric and duodenal LI were 5 approximately 6-fold higher than control group (P < 0.01). (2) Q. or C. used alone showed no effect on gastro-duodenal mucosa, Q. used before MPTP could resist the MPTP-induced mucosa injury, especially in duodenum (P < 0.01). This effectiveness is dose dependent. C. had no effect on gastro-duodenal mucosa protection. (3) The mucosal NO concentration and iNOS activity in MPTP group were lower than that in control, especially in duodenum (P < 0.05). They were negative correlated with LI. CONCLUSION: MPTP peritoneal injection induced significant gastro-duodenal mucosa injury in rat, mediated partially by decreasing the activity of mucosa iNOS and NO concentration. D(4) agonist Q. could resist the effectiveness of MPTP-induced mucosa injury, while the antagonist C. had no effect.