ObjectiveTo explore the effects of naringin on trefoil factor 2 (TFF2) content in serum and gastric mucosa tissue in gastric ulcer rats induced by acetic acid and its therapeutic effects on gastric ulcer. MethodsForty-five rats were randomly divided into normal control group,model control group and naringin high and low dose groups.The acetic acid gastric ulcer model was established by modified okabe method.On the next day,model control group was given 0.9% sodium chloride solution 1 mL·(100 g)-1,naringin low-dose group was given 50 mg·kg-1, and naringin high-dose group was given 100 mg·kg-1,all by gastric perfusion once-daily for 7 days.Gastric ulcer area was measured,and the contents of TFF2 in serum and gastric mucosa tissue were detected by enzyme linked immunosorbent assay (ELISA). ResultsCompared with the model control group,the ulcer index in naringin treatment groups were significantly decreased (P<0.01),and the contents of TFF2 in serum and gastric mucosa tissue were significantly increased (P<0.05).The high dose group was obviously superior to the low dose group (P<0.01). ConclusionNaringin has significant anti-gastric ulcer effects and the mechanism may be associated with the increased content of TFF2 in serum and gastric mucosa tissue.
Fig.1
Pathology of gastric mucosa in four groups of rats(HE staining)
A.normal control group(×10);B.model control group(×40); C.low-dose naringin group(×10);D.high-dose naringin group(×10)
OKABES,AMAGASEK.An overview of acetic acid ulcer models-the history and state of the art of peptic ulcer research[J].,2005,28(8):1321-1341.
Four types of experimental chronic ulcer models, named acetic acid ulcer models, have been developed to examine the healing process of peptic ulcers, screen anti-ulcer drugs, and better evaluate the adverse effects of various anti-inflammatory drugs on the gastrointestinal mucosa. The model easily and reliably produces round, deep ulcers in the stomach and duodenum, allowing acetic acid ulcer production in mice, rats, Mongolian gerbils, guinea pigs, cats, dogs, miniature pigs, and monkeys. These ulcer models highly resemble human ulcers in terms of both pathological features and healing process. The models have been established over the past 35 years and are now used throughout the world by basic and clinical scientists. One of the characteristic features of acetic acid ulcers in rats is the spontaneous relapse of healed ulcers >100 d after ulceration, an endoscopically confirmed phenomenon. Indomethacin significantly delays the healing of acetic acid ulcers, probably by reducing endogenous prostaglandins and inhibiting angiogenesis in ulcerated tissue. Helicobacter pylori significantly delays healing of acetic acid ulcers and causes relapse of healed ulcers at a high incidence in Mongolian gerbils. Anti-secretory drugs (e.g. omeprazole), prostaglandin analogs, mucosal defense agents (e.g. sucralfate), and various growth factors all significantly enhance healing of acetic acid ulcers. Gene therapy with epidermal growth factor and vascular endothelial growth factor applied to the base of acetic acid ulcers in rats is effective in enhancing ulcer healing. Since an inhibitor of nitric oxide syntase prevents ulcer healing, nitric oxide might be involved in the mechanism underlying ulcer healing. We conclude that acetic acid ulcer models are quite useful for various studies related to peptic ulcers.
MAY FE,SEMPLE JI,NEWTON JL,et al.The human two domain trefoil protein,TFF2,is glycosylated in vivo in the stomach[J].,2000,46(4) :454-459.
Background-TFF2, a member of the trefoil factor family (TFF) of peptides, is a secreted protein of 106 amino acids that is expressed in mucous neck cells of the fundus and glands at the base of the antrum in normal human stomach. TFF2 is also detected at high concentrations around sites of ulceration. It is protective against mucosal damaging agents and stimulates cell motility. Aims-To measure the expression of TFF2 in normal human stomach and its secretion into gastric juice. Methods-TFF2 cDNA was amplified by reverse transcription polymerase chain reaction from gastric mucosa and sequenced. Gastric juice or cytosol, prepared from gastric mucosa, was obtained from individuals with macroscopically normal stomachs. TFF2 concentrations were measured by quantitative western transfer analysis. Results-Sequencing of TFF2 cDNA revealed a single amino acid change from the published sequence. Significant amounts of 12 kDa TFF2 were detected in human gastric juice. Larger quantities of a protein of higher apparent molecular mass were also detected. This was shown to be N-glycosylated TFF2 using the endoglycosidase, peptide-N-Gycosidase F. The majority of TFF2 in normal gastric mucosa was also glycosylated. Conclusions-Human TFF2 is glycosylated via an N-linkage, presumably on Asn
YUY,JIA TZ,CAIQ,et al.Comparison of the anti-ulcer activity between the crude and bran-processed Atractylodes lancea in the rat model of gastric ulcer induced by acetic acid[J].,2015,160(3):211-218.
The rhizome of(AL, Compositae, Chinese name: Cangzhu; Japanese name: Sou-ju-tsu) has been used traditionally for the treatment of various diseases such as digestive disorders, rheumatic diseases, and influenza in China, Korea and Japan. The crude AL and AL bran-processed are both listed in the Chinese Pharmacopoeia. However, the differences between the effects of the crude and AL bran-processed on gastric ulcer were poorly understood, and the mechanisms for the treatment of gastric ulcer were not clear. This study aimed at comparing the anti-ulcer effects between the crude AL and AL processed in acetic acid induced model in rats and evaluating the mechanisms of action involved in the anti-ulcer properties of AL.The model of gastric ulcer was imitated by acetic acid in rats, and AL was gavaged. The serum and gastric tissues were collected. The levels of epidermal growth factor (EGF), trefoil factor2 (TFF2), tumor necrosis factor-伪 (TNF-伪), interleukin 6, 8 (IL-6, 8) and prostaglandin E(PGE) in serum and gastric tissues were determined by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of EGF, TFF2, TNF-伪, and IL-8 in stomach were analyzed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, histopathological changes were evaluated by hematoxylin and eosin (HE) stain. The protein expressions of EGF, TFF2, TNF-伪, and IL-8 were examined by immunohistochemistry in stomach.The results demonstrated that the damage of gastric tissue was obviously alleviated and the productions of TNF-伪, IL-8, IL-6, and PGEand the mRNA expressions of TNF-伪, and IL-8 were notably inhibited. Furthermore, the productions of EGF and TFF2 and the mRNA expressions of EGF and TFF2 were significantly stimulated by both crude AL and AL processed in a dose-dependent manner. Compared with the crude AL, the processed AL was more effective.The AL processed had more satisfactory effects in treatment of gastric-ulcer than the crude AL. The anti-ulcer effects of AL could be attributed to the anti-inflammatory propertiesdown-regulating TNF-伪, IL-8, IL-6 and PGEand to the gastroprotective effectsup-regulating EGF and TFF2.
Comparison of the anti-ulcer activity between the crude and bran-processed Atractylodes lancea in the rat model of gastric ulcer induced by acetic acid