Influence of gastric colonization with Candida albicans on ulcer healing in rats: effect of ranitidine, aspirin and probiotic therapy

OBJECTIVE: Candida albicans frequently inhabits the gastrointestinal tract of humans leading to gastrointestinal candidiasis, especially following suppression of gastric acidity, but studies on the relation between this fungal infection and gastric pathology are limited due to lack of convenient animal models resembling Candida infection in humans. MATERIAL AND METHODS. We compared the effects of C. albicans and vehicle inoculation on gastric secretion and healing of gastric ulcers induced by acetic acid in rats treated with 1) ranitidine (30 mg kg(-1) day(-1) s.c.) and 2) aspirin (ASA) (60 mg kg(-1) day(-1) i.g.) with or without probiotic bacteria Lactobacillus acidophillus. At day 0 and at 4, 15 and 25 days after ulcer induction, the ulcer area, the gastric blood flow (GBF), the quantitative gastric cultures of Candida and the expression of mRNAs for pro-inflammatory cytokines IL-1beta and TNF-alpha and growth factors EGF and TGFalpha were assessed in the gastric mucosa. RESULTS: Gastric acid output was reduced by over 40% soon after Candida inoculation and this effect persisted during all time intervals tested. The area of ulcers in control rats significantly decreased at day 15 and the ulcers disappeared almost completely after 25 days of their induction. In contrast, the ulcers were present until day 25 in Candida-inoculated rats followed by a fall in GBF and a rise in plasma gastrin levels, these effects being significantly attenuated by the co-treatment with Lactobacillus. Candidiasis was accompanied by up-regulation of mRNA for IL-1beta, TNF-alpha, EGF and TGFalpha and a significant increment in plasma IL-1beta and TNF-alpha levels. CONCLUSIONS: 1) Persistent colonization with Candida could be achieved in rats treated with antisecretory agents or non-steroidal anti-inflammatory drugs (NSAIDs) such as ASA; 2) candidiasis reduces gastric acid secretion, while delaying ulcer healing possibly due to the impairment in GBF in the ulcer area and enhanced expression and release of IL-1beta and TNFalpha and 3) probiotic therapy could be useful in the treatment against the deleterious action of fungal infection on the healing of pre-existing gastric ulcers.     

Expression and immunolocalization of heat shock proteins in the healing of gastric ulcers in rats

BACKGROUND: Heat shock proteins are induced when cells are subjected to noxious stimuli. They afford cytoprotection and increase the resistance of the tissue to damage. However, their roles in the healing of gastric ulcers have not been well established. In this study, the expression and immunolocalization of three heat shock proteins (HSPs); namely inducible HSP70 (iHSP70), HSP47, and HSP32 during ulcer healing were investigated in rats with gastric ulcer. METHODS: Gastric ulcers (kissing ulcers) were induced by luminal application of acetic acid solution. Gastric tissue samples were obtained from the ulcer base, ulcer margin, and non-ulcerated area around the ulcer margin at different time intervals after ulcer induction. The protein levels and distributions of HSPs were analyzed with Western blotting and immunohistochemical methods, respectively. RESULTS: It was found that all HSPs were expressed in normal, non-ulcerated, and gastric ulcer tissues. HSP32 was elevated during inflammation (1-8 days after ulcer induction), while HSP47 expression was exacerbated at the ulcer base and margin during ulcer healing (3-12 days). Decreased expression of iHSP70 was observed at the ulcer base immediately after ulcer induction, but returned to normal level by the end of the healing stage (8-12 days). Inducible HSP70 was found distributed in the gastric glands and injured tissues in the inflamed areas. Wide distribution of HSP47 was detected in granulation tissues and collagen producing cells, while HSP32 was localized in the gastric glands and inflammatory cells. CONCLUSIONS: The findings indicate that iHSP70, HSP47, and HSP32 play different roles during ulcer healing. HSP32 seems to act as an inflammatory defensive factor, and HSP47 as a collagen-specific molecular chaperon contributing significantly to gastric ulcer healing. However, the role of iHSP70 in the ulcer healing process is still undefined.     

Influence of bacterial lipopolysaccharide on healing of chronic experimental ulcer in rat.

BACKGROUND: Lipopolysaccharides (LPS) are major components of the outer membrane of Gram-negative bacteria, which play a central role as potent endotoxins in the pathogenesis of the Gram-negative septicaemia. Although it is well known that large amounts of endotoxin may produce haemorrhagic lesions in the stomach, the effect of LPS on ulcer healing has not been fully clarified. The aim of the present study was to examine the effect of parenteral injection of LPS at different doses on the course of ulcer healing in rats. METHODS: Gastric ulcers were induced in Wistar rats by serosal application of an acetic acid area. After ulcer induction, vehicle (saline) or E. coli-LPS was injected at various doses (0.1, 1 and 5 mg/kg i.p.) for 7 days. The animals were sacrificed on day 8 after ulcer induction and the following parameters were analysed; ulcer area (planimetry), gastric blood flow (GBF) (H2 gas clearance method), gastric secretion, plasma levels of proinflammatory cytokines such as IL-1beta and TNFalpha, mucosal gene expression for cyclooxygenases (COX-1/-2), apoptosis-related proteins (Bax, Bcl-2), TNFalpha, IL-1beta and vascular endothelial growth factor (VEGF). RESULTS: Daily parenteral challenge with LPS resulted in a dose-dependent delay in ulcer healing with maximum observed at a dose of 5 mg/kg (12.14 +/- 1.2 mm2 versus 5.18 +/- 0.8 mm2 in the control group). The impairment of ulcer healing in LPS-treated rats was associated with a significant decrease in GBF, increased mRNA expression for IL-1beta, TNFalpha, the rise in plasma IL-1beta and TNFalpha levels, an overexpression of COX-2 and VEGF and imbalance in the ratio between pro-apoptotic Bax and antiapoptotic Bcl-2. The daily administration of 50 mg/kg pentoxifylline by itself failed to accelerate the ulcer healing but attenuated the deleterious effects of LPS on this healing. CONCLUSIONS: 1) Bacterial endotoxin impairs ulcer healing through the decrease in gastric mucosal blood flow, increased expression and release of proinflammatory cytokines IL-1beta and TNFalpha, the imbalance between pro- and anti-apoptotic members of Bcl-2 family via downregulation of antiapoptotic bcl-2, and 2) endotoxin leads to upregulation of genes for VEGF and COX-2, which fail to accelerate the ulcer healing.     

Acid regulates inflammatory response in a rat model of induction of gastric ulcer recurrence by interleukin 1beta

BACKGROUND: In a previous study we showed that interleukin 1beta (IL-1beta) caused recurrence of gastric ulcers in rats, and that adhesion molecules (intercellular adhesion molecule 1 and leucocytic beta2 integrins) play a role in this recurrence. Although gastric acid plays an important role in many types of gastric injuries, including peptic ulcer recurrence, the mechanism(s) remains unclear. AIMS: To examine the involvement of gastric acid in induction of ulcer recurrence by IL-1beta, and to investigate the role of gastric acid in inflammatory responses during ulcer recurrence. METHODS: Rats with healed ulcers were used. Rats were given 1 microg/kg IL-1beta intraperitoneally. Another group of rats was given 20 mg/kg omeprazole for three days to inhibit acid secretion, and received IL-1beta 20 hours after the first administration of omeprazole. They were then given 0.15 N HCl or vehicle at 0, 12, 24, and 36 hours after IL-1beta treatment. Some rats were given acid alone at the same time points. Expression of adhesion molecules was examined immunohistochemically and concentrations of IL-1beta and tumour necrosis factor alpha (TNF-alpha) were measured by ELISA in scar tissue 24 hours after IL-1beta treatment. RESULTS: IL-1beta increased expression of adhesion molecules and concentrations of IL-1beta and TNF-alpha in scar tissue by 24 hours after IL-1beta treatment, and nine of 11 healed ulcers had recurred by 48 hours. Omeprazole inhibited the effects of IL-1beta. HCl acid abolished the inhibitory effects of omeprazole. Acid alone affected neither expression of adhesion molecules nor cytokine concentrations, and did not cause recurrence. CONCLUSIONS: Gastric acid is required for recurrence of gastric ulcers caused by IL-1beta, and gastric acid stimulates the inflammatory process in scarred mucosa during ulcer recurrence.     

Influence of Bacterial Lipopolysaccharide on Healing of Chronic Experimental Ulcer in Rat

Background: Lipopolysaccharides (LPS) are major components of the outer membrane of Gramnegative bacteria, which play a central role as potent endotoxins in the pathogenesis of the Gram-negative septicaemia. Although it is well known that large amounts of endotoxin may produce haemorrhagic lesions in the stomach, the effect of LPS on ulcer healing has not been fully clarified. The aim of the present study was to examine the effect of parenteral injection of LPS at different doses on the course of ulcer healing in rats. Methods: Gastric ulcers were induced in Wistar rats by serosal application of an acetic acid area. After ulcer induction, vehicle (saline) or E. coli -LPS was injected at various doses (0.1, 1 and 5 mg/kg i.p.) for 7 days. The animals were sacrificed on day 8 after ulcer induction and the following parameters were analysed; ulcer area (planimetry), gastric blood flow (GBF) (H 2 gas clearance method), gastric secretion, plasma levels of proinflammatory cytokines such as IL-1 β and TNF α , mucosal gene expression for cyclooxygenases (COX-1/-2), apoptosis-related proteins (Bax, Bcl-2), TNF α , IL-1 β and vascular endothelial growth factor (VEGF). Results: Daily parenteral challenge with LPS resulted in a dose-dependent delay in ulcer healing with maximum observed at a dose of 5 mg/kg (12.14 ± 1.2 mm2 versus 5.18 ± 0.8 mm2 in the control group). The impairment of ulcer healing in LPS-treated rats was associated with a significant decrease in GBF, increased mRNA expression for IL-1 β , TNF α , the rise in plasma IL-1 β and TNF α levels, an overexpression of COX-2 and VEGF and imbalance in the ratio between pro-apoptotic Bax and antiapoptotic Bcl-2. The daily administration of 50 mg/kg pentoxifylline by itself failed to accelerate the ulcer healing but attenuated the deleterious effects of LPS on this healing. Conclusions: 1) Bacterial endotoxin impairs ulcer healing through the decrease in gastric mucosal blood flow, increased expression and release of proinflammatory cytokines IL-1 β and TNF α , the imbalance between pro- and anti-apoptotic members of Bcl-2 family via downregulation of antiapoptotic bcl-2, and 2) endotoxin leads to upregulation of genes for VEGF and COX-2, which fail to accelerate the ulcer healing.     

模拟失重对大鼠实验性胃溃疡愈合的影响

目的:探讨模拟失重对乙酸诱导的大鼠实验性胃溃疡愈合的影响及可能机制.方法:32只SD大鼠随机分为4组,即尾部悬吊7d组、尾部悬吊14d组和相应的同步对照组.采用乙酸烧灼法制备大鼠慢性胃溃疡模型,造模后第3天悬吊组大鼠采用尾悬吊法建立模拟失重动物模型.游标卡尺检测胃溃疡面积,电镜下观察再生黏膜结构,放免法检测胃液EGF含量,观察大鼠胃溃疡愈合分期.结果:与对照7d组相比,悬吊7d组大鼠溃疡面积明显增大(6.0mm2±1.7mm2vs2.2mm2±0.7mm2,t=5.661,P<0.01),溃疡分期明显降低(χ2=12.771,P<0.01);与对照14d组相比,悬吊14d组溃疡面积明显增大(3.0mm2±1.2mm2vs1.1mm2±0.4mm2,t=4.233,P<0.01),胃液EGF含量明显增高(0.155ng/mL±0.052ng/mLvs0.103ng/mL±0.019ng/mL,t=2.635,P<0.05);与悬吊7d组比较,悬吊14d组溃疡面积明显减小(3.0mm2±1.2mm2vs6.0mm2±1.7mm2,t=3.805,P<0.01),胃液EGF含量明显降低(0.155ng/mL±0.0...     

Influence of gastric colonization with Candida albicans on ulcer healing in rats: Effect of ranitidine,aspirin and probiotic therapy

Objective. Candida albicans frequently inhabits the gastrointestinal tract of humans leading to gastrointestinal candidiasis, especially following suppression of gastric acidity, but studies on the relation between this fungal infection and gastric pathology are limited due to lack of convenient animal models resembling Candida infection in humans. Material and methods. We compared the effects of C. albicans and vehicle inoculation on gastric secretion and healing of gastric ulcers induced by acetic acid in rats treated with 1) ranitidine (30 mg kg^?1 day^?1 s.c.) and 2) aspirin (ASA) (60 mg kg^?1 day^?1 i.g.) with or without probiotic bacteria Lactobacillus acidophillus. At day 0 and at 4, 15 and 25 days after ulcer induction, the ulcer area, the gastric blood flow (GBF), the quantitative gastric cultures of Candida and the expression of mRNAs for pro-inflammatory cytokines IL-1β and TNF-α and growth factors EGF and TGFα were assessed in the gastric mucosa. Results. Gastric acid output was reduced by over 40% soon after Candida inoculation and this effect persisted during all time intervals tested. The area of ulcers in control rats significantly decreased at day 15 and the ulcers disappeared almost completely after 25 days of their induction. In contrast, the ulcers were present until day 25 in Candida-inoculated rats followed by a fall in GBF and a rise in plasma gastrin levels, these effects being significantly attenuated by the co-treatment with Lactobacillus. Candidiasis was accompanied by up-regulation of mRNA for IL-1β, TNF-α, EGF and TGFα and a significant increment in plasma IL-1β and TNF-α levels. Conclusions. 1) Persistent colonization with Candida could be achieved in rats treated with antisecretory agents or non-steroidal anti-inflammatory drugs (NSAIDs) such as ASA; 2) candidiasis reduces gastric acid secretion, while delaying ulcer healing possibly due to the impairment in GBF in the ulcer area and enhanced expression and release of IL-1β and TNFα and 3) probiotic therapy could be useful in the treatment against the deleterious action of fungal infection on the healing of pre-existing gastric ulcers.     

Healing of duodenal ulcers is not impaired by indomethacin or rofecoxib,the selective COX-2 inhibitor,in rats

BACKGROUND/AIM: Studies have demonstrated an important role for endogenous PG and NO in the healing of chronic gastric ulcers. We investigated the effects of COX and NOS inhibitors on the healing of duodenal ulcers, in comparison with gastric ulcers, in rats. METHODS: Gastric and duodenal ulcers were induced by serosal application of acetic acid (0.1 ml of 100% acetic acid) for 60 and 20 s, respectively. Indomethacin (a nonselective COX inhibitor) or rofecoxib (a selective COX-2 inhibitor) was given p.o. once daily for 14 days from 3 days after ulcer induction, while N(G)-nitro-L-arginine methyl ester (L-NAME: a nonselective NOS inhibitor) or aminoguanidine (a relatively selective iNOS inhibitor) was given s.c. twice daily during this period. RESULTS: Both gastric and duodenal ulcers induced by acetic acid healed spontaneously within 17 days to a minimal size. Daily administration of indomethacin or rofecoxib significantly delayed the healing of gastric but not duodenal ulcers. In contrast, the healing of both gastric and duodenal ulcers was delayed by repeated administration of either L-NAME or aminoguanidine. Ulceration markedly increased the PGE(2) content of the ulcerated mucosa in both the stomach and duodenum, and the increased PG biosynthetic response was inhibited by either indomethacin or rofecoxib in both tissues. The expression of both COX-2 and iNOS mRNAs was upregulated in the ulcerated mucosa of the stomach and duodenum. CONCLUSION: These results suggest that COX-2/PG is actively involved in the healing of gastric but not duodenal ulcers, although the mRNA for COX-2 is expressed in the duodenal mucosa after ulceration, as potently as in the gastric mucosa. In contrast, NO produced by both cNOS and iNOS plays a role in the healing of both gastric and duodenal ulcers.     

Expression and activities of three inducible enzymes in the healing of gastric ulcers in rats

AIM: To explore the roles of nitric oxide synthase (NOS), heme oxygenase (HO) and cyclooxygenase (COX) in gastric ulceration and to investigate the relationships of the expression and activities of these enzymes at different stages of gastric ulceration. METHODS: Gastric ulcers (kissing ulcers) were induced by luminal application of acetic acid. Gastric tissue samples were obtained from the ulcer base, ulcer margin, and non-ulcerated area around the ulcer margin at different time intervals after ulcer induction. The mRNA expression and protein levels of inducible and constitutive isoforms of NOS, HO and COX were analyzed with RT-PCR and Western blotting methods. The activities of the total NOS, inducible NOS (iNOS), HO, and COX were also determined. RESULTS: Differential expression of inducible iNOS, HO-1 and COX-2 and enzyme activities of NOS, HO and COX were found in the gastric ulcer base. High iNOS expression and activity were observed on day 1 to day 3 in severely inflamed ulcer tissues. Maximum expressions of HO-1 and COX-2 and enzyme activities of HO and COX lagged behind that of iNOS, and remained at high levels during the healing phase. CONCLUSION: The expression and activities of inducible NOS, HO-1 and COX-2 are found to be correlated to different stages of gastric ulceration. Inducible NOS may contribute to ulcer formation while HO-1 and COX-2 may promote ulcer healing.     

Influence of Capsaicin-Sensitive Afferent Fibers on Acetic Acid-Induced Chronic Gastric Ulcers in Rats

Tramontana M. Renzi D, Calabró A. Panerai C. Milani S, Surrenti C, Evangelista S. Influence of capsaicin-sensitive afferent fibers on acetic acid-induced chronic gastric ulcers in rats. Scand J Gastroenterol 1994;29:406-413.

Accumulating evidence indicates that capsaicin-sensitive afferent fibers play a pivotal role in acute gastroprotection. However, whether they also influence healing of chronic gastric ulcers is still unknown. The effects of ablation of sensory neurons on acetic acid-induced chronic gastric ulcers in rats were investigated at morphologic and biochemical levels by computerized imaging analysis of the ulcerated area, histologic examination, and neuropeptide determination. Afferent nerve ablation, as a result of treating rats with a neurotoxic dose of capsaicin (50 + 50 mg/kg subcutaneously over 2 days), produced a significant increase in the ulcer area at 1 and 2 weeks after acetic acid injection. The delay in ulcer healing was associated with a marked and persistent decrease in tissue calcitonin gene-related peptide-like immunoreactivity. whereas gastric vasoactive intestinal polypeptide was unaffected by capsaicin pretreatment. Histologically, as compared with control rats, capsaicin-desensitized animals only differed in a slight increase in the inflammatory infiltrate during the early phase of ulcer formation. These findings suggest that capsaicin-sensitive afferent fibers may play a role in the healing of chronic experimental gastric ulcers in rats, but the underlying mechanisms remain to be elucidated and deserve further investigation.     

Influence of age on natural and delayed healing of experimentally-induced gastric ulcers in rats

This study aimed to investigate the effect of age on natural ulcer healing and delayed ulcer healing induced by nonsteroidal antiinflammatory drugs, using a rat model. Gastric ulcers were induced in young, adult, and aged rats using serosal or mucosal (kissing ulcers) application of acetic acid. Rats were treated with indomethacin 1 mg/kg/day subcutaneously or vehicle for two weeks. Ulcers were assessed by macroscopic and histological measurements of ulcer size. Ulcer induction was affected by age. Aged rats developed significantly smaller ulcers when induced by serosal application of acetic acid and significantly larger ulcers from mucosal application of acetic acid. However, measurements of ulcer size from both models showed no age-related differences in natural ulcer healing. Similarly, indomethacin-induced delayed gastric ulcer healing was not effected by age. We conclude that there are age-related differences in the development of gastric ulcers but there are no age-related differences in natural or delayed ulcer healing in rats.This study was supported by grants from the Sandoz Foundation for Gerontological Research, Australia and Perpetual Trustees, Australia.     

Mouse model of gastric infection with cytotoxin-expressing strain of Helicobacter pylori in studying of pathogenesis of chronic gastric ulcer

Abstract Helicobacter pylori is a major risk factor for peptic ulcer, but studies on the role of H. pylori infection in gastric pathology are limited due to lack of convenient models resembling H. pylori infection in humans. We studied the effects of inoculation of conventional BALB/c mice with a toxigenic (cytotoxin associated gene A (cagA)+ and vacuolating cytotoxin gene A (vacA+) H. pylori strain on the course of healing of gastric ulcers. Following inoculation of toxigenic H. pylori or vehicle, gastric ulcers were produced in mice, which were then killed either at day 0 or after 2, 4, 7, 14 or 28 days and ulcer area and gastric blood flow (GBF) were determined. Gastric secretions from mice with chronic gastric fistulae were studied before and after inoculation with toxigenic H. pylori or vehicle (saline). The area (7 mm²) of ulcers in control mice decreased gradually and disappeared almost completely after 14 or 28 days. The ulcers in H. pylori-infected mice were present at all test days, showing a larger area than in vehicle control animals. The GBF in control mice rose gradually with decreasing ulcer size, being significantly higher at the ulcer margin than the ulcer crater. In contrast, the GBF in H. pylori-infected mice was significantly lower at the ulcer area than that in the vehicle controls but, again, the GBF at the ulcer margin was always higher than at the ulcer crater. Gastric acid output was reduced by more than 50% immediately after H. pylori inoculation and was accompanied by a significant increase in plasma gastrin release and a fall in gastric luminal somatostatin content. These secretory changes persisted at all test days. Oedema/congestion of surface epithelium appeared after 7 days and mucosal inflammatory infiltration appeared after 14 days, to further increase after 28 days, upon the induction of ulcer. Plasma interleukin (IL)-Iß and IL-12 were significantly elevated above the initial values compared with controls. Conventional mice with gastric ulcers can be successfully infected with an H. pylori strain expressing cagA and vacA cytotoxin and this infection markedly delays healing of the ulcers, probably due to the fall in GBF in the ulcer area, mucosal inflammation, cytokine release and impairment of the gastrin-somatostatin link.     

Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats

AIM: To compare the effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing. METHODS: Male Spraque-Dawley rats (n=48) were divided into four groups. Groupl served as control group, group 2 as gastric ulcer group without treatment, groups 3 and 4 as gastric ulcer treatment groups with sucralfate and Aloe vera. The rats from each group were divided into 2 subgroups for study of leukocyte adherence, TNF-αand IL-10 levels and gastric ulcer healing on days 1 and 8 after induction of gastric ulcer by 20% acetic acid. RESULTS: On day 1 after induction of gastric ulcer, the leukocyte adherence in postcapillary venule was significantly (P<0.05) increased in the ulcer groups when compared to the control group. The level of TNF-αwas elevated and the level of IL-10 was reduced. In the ulcer groups treated with sucralfate and Aloe vera, leukocyte adherence was reduced in postcapillary venule. The level of IL-10 was elevated, but the level of TNF-αhad no significant difference. On day 8, the leukocyte adherence in postcapillary venule and the level of TNF-αwere still increased and the level of IL-10 was reduced in the ulcer group without treatment. The ulcer treated with sucralfate and Aloe vera had lower leukocyte adherence in postcapillary venule and TNF-αlevel. The level of IL-10 was still elevated compared to the ulcer group without treatment. Furthermore, histopathological examination of stomach on days 1 and 8 after induction of gastric ulcer showed that gastric tissue was damaged with inflammation. In the ulcer groups treated with sucralfate and Aloe vera on days 1 and 8, gastric inflammation was reduced, epithelial cell proliferation was enhanced and gastric glands became elongated. The ulcer sizes were also reduced compared to the ulcer group without treatment. CONCLUSION: Administration of 20% acetic acid can induce gastric inflammation, increase leukocyte adherence in postcapillary venule and TNF-αlevel and reduce IL-10 level. Aloe vera treatment can reduce leukocyte adherence and TNF-αlevel, elevate IL-10 level and promote gastric ulcer healing.     

Chronicity of acetic acid ulcer in the rat stomach

Experimental gastric ulcers, produced by submucosal injection of acetic acid in rats were studied in relationship to healing. Small ulcers healed completely within 40 days after induction; moderately severe ulcers were sometimes found at 150 days, and probably resulted from repeated healing and reulceration. Large severe ulcers partially healed and then became reexacerbated; they frequently increased in size up to 250 days, thus resembling chronic gastric lesions. Throughout the experimental periods, adhesion of the ulcer base with adjacent organs and delayed gastric emptying were found in most animals. After ulceration, an increase in gastric volume and acid output and a decrease in protease activity of gastric contents were found in chronic fistula rats with experimental ulcers. The secretory changes observed here may have been secondary to gastric ulceration and/or delayed gastric emptying. The factors responsible for the reexacerbation of the experimental ulcer remain unidentified.Supported by the William H. Rorer Gastroenterology Research Fund.     

健中愈疡片对乙酸诱导胃溃疡大鼠表皮生长因子及其受体表达的影响

[目的]观察健中愈疡片对乙酸诱导胃溃疡大鼠血清表皮生长因子（EGF）水平和胃溃疡边缘表皮生长因子受体（EGFR）表达的影响。[方法]制备乙酸诱导大鼠胃溃疡模型，分别予健中愈疡片、雷尼替丁和0．85％氯化钠液治疗14d，用放射免疫分析法测定大鼠血清EGF水平，免疫组织化学染色法检测胃溃疡边缘EGFR表达。[结果]造模3d时，胃溃疡模型组大鼠的血清EGF水平明显高于正常对照组，胃溃疡边缘EGFR表达比正常对照组明显增加。治疗14d后，与雷尼替丁组和0．85％氯化钠液组比较，健中愈疡片组的血清EGF水平显著减少（P〈0．01），而胃溃疡边缘EGFR表达显著增加（P〈0．01）。[结论]血清EGF水平可以作为反映胃肠黏膜完整性的一个监控指标，健中愈疡片能够减少血清EGF水平和增加胃溃疡边缘EGFR表达，这可能是其加速乙酸诱导胃溃疡愈合的主要作用机制。