Healing of acetic acid-induced gastric ulcer and gastric mucosal PGI2 level in rats

The present study was designed to investigate the changes in gastric mucosal PGI₂ level accompanying the healing of acetic acid-induced gastric ulcers in rats. The ulcers, which were observed with an endoscope, were found to undergo periods of decrease, healing and exacerbation during the rat's lifetime. The phases were categorized as follows: (1) the reduction period (days 3–50 after ulcer induction, corresponding to 7–14 weeks of age), (2) healing period (days 35–150 after ulcer induction, corresponding to 12–29 weeks of age), (3) first exacerbation period (days 35–231 after ulcer induction, corresponding to 12–40 weeks of age), (4) inactive period (days 231–365 after ulcer induction, corresponding to 40–60 weeks of age), and (5) second exacerbation period (days 365–550 after ulcer induction, corresponding to 60–86 weeks of age). In normal rats, the level of gastric mucosal PGI₂ gradually increased with aging between 7 and 20 weeks, then decreased up to 40 weeks. The PGI₂ level in the 60-week-old rat did not differ from that in the 40-week-old rat. The PGI₂ level was the lowest in the 86-week-old rat. In ulcer-bearing rats, the PGI₂ level showed the same pattern of change as that in normal rats, but the level was higher. The above results indicated a marked decrease in PGI₂ level between 20 and 40 weeks of age and between 60 and 86 weeks of age in normal and ulcer-bearing rats. These periods corresponded closely to the first and second exacerbation periods, respectively. Thus, it can be postulated that ulcer aggravation may be caused by a marked decrease in gastric mucosal PGI₂ generation.     

Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats

AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP) leaves on gastric ulcer healing.METHODS In this rat study involving males, intact(cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%), intact females(85.22%), and ovariectomized females(65.47%), confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed.CONCLUSION In gastric ulcers, HEEP-induced healing(modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.     

牛磺酸对大鼠幽门结扎型胃溃疡的影响

目的:探讨牛磺酸对大鼠幽门结扎型胃溃疡的影响及其机制.方法:采用结扎大鼠幽门的方法建立大鼠胃溃疡模型.45只Wistar大鼠随机分为三组,即正常对照组、溃疡模型组和牛磺酸处理组.经6 h后各组大鼠处死,检测三组大鼠胃黏膜溃疡指数(UI)、胃液总酸度、胃蛋白酶活性和壁细胞H~ ,K~ -ATP酶活性.结果:与正常对照组相比,溃疡模型组大鼠UI值(35.3±3.7 vs,P<0.01)和胃液总酸度增大(28.56±3.81 mmol/L vs 20.34±4.40 mmol/L,P<0.01),同时胃液胃蛋白酶活性[7.58±1.58μg/(mL·min)vs 5.83±1.22μg/(mL·min),P<0.01]和壁细胞H~ ,K~ -ATP酶活性升高(8.86±1.50 U/mg vs 6.95±1.03 U/mg,P<0.01);而应用牛磺酸则减轻了大鼠应激性胃黏膜损伤,UI值(15.4±3.6 vs 35.3±3.7,P<0.01)和胃液总酸度减小(19.58±3.68 mmol/L vs 28.56±3.81 mmol/L,P<0.01),胃液胃蛋白酶活性[6.36±1.45μg/(mL·min)vs 7.58±1.58μg/(mL·min),P<0.05]和壁细胞H~ ,K~ -ATP酶活性(7.62±1.46 U/mg vs 8.86±1.50 U/mg,P<0.05)降低.结论:牛磺酸具有抗大鼠幽门结扎型胃溃疡的作用,其机制可能与抑制胃酸及胃蛋白酶分泌有关.     

Effects of NC-1300, a gastric proton pump inhibitor,on healing of acetic acid-induced gastric ulcers in rats

Effects of NC-1300 (a gastric proton pump inhibitor) on healing of experimental chronic gastric ulcers induced in rats were studied. Gastric ulcers were induced by the submucosal injection of 20% acetic acid (0.03 ml) into the antral-oxyntic border of the anterior wall of male Donryu rats (260–280 g). The healing of acetic acid ulcers was delayed by the daily subcutaneous administration of indomethacin (1 mg/kg) for two or four weeks after ulceration. Aggravation of healed ulcers was evoked by subcutaneous administration of indomethacin (1 mg/kg) once daily for four weeks to rats with four-week-old ulcers. Oral administration of NC-1300 (10, 30, or 100 mg/kg) once daily for two or four weeks after ulceration dose-dependently accelerated both natural and delayed healing of acetic acid ulcers. When the period of administration was extended from two to four weeks, the ED₅₀ values (the dose reducing the ulcerated area by 50%) were decreased from 36.5 to 13.5 mg/ kg in natural healing and from 76.0 to 23.0 mg/kg in delayed healing. Aggravation of four-week-old ulcers by indomethacin was significantly prevented by daily administration of NC-1300 (30 or 100 mg/kg) for four weeks. Acetic acid ulcers that were healed with NC-1300 given for four weeks after ulceration remained healed for four to eight weeks after the cessation of drug administration. A single administration of NC-1300 to normal rats and repeated administration of NC-1300 to rats with acetic acid ulcers for four weeks after ulceration caused the same degree of inhibition of gastric acid secretion. Reduction in the area of ulceration and inhibition of gastric acid secretion by NC-1300 were significantly correlated in the indomethacin-treated animals. We conclude that NC-1300 markedly accelerates the healing of chronic gastric ulcers and prevents aggravation of the healed ulcers, presumably through antisecretory activities.     

Protective role of metallothionein in stress-induced gastric ulcer in rats

AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO_4 (an MT inducer) treatment, WIR+ZnSO_4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry. RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO_4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower. CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stressinduced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress-induced gastric ulcers.     

福建省胃癌和十二指肠溃疡患者白细胞介素1基因多态性的比较

目的了解福建省胃癌和十二指肠溃疡患者中白细胞介素1（IL-1）基因多态性的分布并进行比较。方法病理确诊的144例胃癌及排除非甾体类抗炎药服用史的102例十二指肠溃疡患者，采用PCR—RFLP分析检测IL-1基因多态性。结果（1）胃癌患者中，IL-1B-511基因型CC、CT、rlT分别占18．1％、48．6％和33，3％，IL-1RN等位基因检测到A1、A2、A4三种，基因型A1／A1、A1／A4、A1／A2、A2／A2分别占88．9％、1．4％、9．0％、0，7％；十二指肠溃疡患者中，IL-1B-511基因型CC、CT、TT分别占19．6％、59，8％和20．6％，IL-1RN等位基因检测到A1、A2两种，基因型A1／A1、A1／A2分别占90，2％、9，8％。（2）IL．1B-511 TT基因型在胃癌患者中的比例与在十二指肠溃疡患者中的比例差异显著（x^2=4.806，P=0．028）；不同IL-1 RN基因型在胃癌的比例与在十二指肠溃疡中的比例无统计学差异。结论福建省胃癌和十二指肠溃疡患者IL-1基因型均以IL-1B-511基因CT型、IL-1RN基因型以A1／A1为主。IL-1 B-511 TT基因型可能与福建省胃癌的高发有关。     

三叶因子2基因治疗对实验性大鼠胃溃疡愈合影响的研究

目的探讨三叶因子2(TFF2)基因治疗对实验性大鼠胃溃疡的疗效及其机制。方法2005-06-10—2006-03-15南方医科大学南方医院消化病研究所将48只雄性Wistar大鼠随机分为2组,治疗组24只,对照组24只。治疗组每只应用pcDNA3.1g TFF2100μg,对照组每只应用等容积pcDNA3.1g TFF2100μg,均在造模时经胃壁浆膜下注入。用药后分别在第3、7、14天处死动物,测量大鼠胃溃疡指数、胃总酸度及黏液糖蛋白量的变化。结果在应用pcDNA3.1g TFF2的第3天,治疗组和对照组比较,各项指标差异无统计学意义(P>0.05);第7天,治疗组的黏液糖蛋白量显著增加,与对照组比较差异有统计学意义(P<0.01)。第14天,治疗组的溃疡面积显著缩小,与对照组比较差异有统计学意义(P<0.01);治疗组黏液糖蛋白量有所下降,不过与对照组比较差异也有统计学意义(P<0.05);而治疗组的胃总酸度变化不大,与对照组比较差异无统计学意义(P>0.05)。结论TFF2基因治疗对实验性大鼠胃溃疡愈合有促进作用,增加胃黏液糖蛋白的分泌是其促进溃疡愈合的机制之一,而与抑制胃酸分泌无关。     

三叶因子2基因治疗对实验性大鼠胃溃疡愈合影响的研究

目的 探讨三叶因子2（TFF2）基因治疗对实验性大鼠胃溃疡的疗效及其机制。方法2005—06-10-2006—03—15南方医科大学南方医院消化病研究所将48只雄性Wistar大鼠随机分为2组，治疗组24只，对照组24只。治疗组每只应用pcDNA3．1g＋TFF2 100μg，对照组每只应用等容积pcDNA3．1g＋TFF2 100μg，均在造模时经胃壁浆膜下注入。用药后分别在第3、7、14天处死动物，测量大鼠胃溃疡指数、胃总酸度及黏液糖蛋白量的变化。结果在应用pcDNA3．1g＋TFF2的第3天，治疗组和对照组比较，各项指标差异无统计学意义（P〉0．05）；第7天，治疗组的黏液糖蛋白量显著增加，与对照组比较差异有统计学意义（P〈0．01）。第14天，治疗组的溃疡面积显著缩小，与对照组比较差异有统计学意义（P〈0．01）；治疗组黏液糖蛋白量有所下降，不过与对照组比较差异也有统计学意义（P〈0．05）；而治疗组的胃总酸度变化不大，与对照组比较差异无统计学意义（P〉0.05）。结论 TFF2基因治疗对实验性大鼠胃溃疡愈合有促进作用，增加胃黏液糖蛋白的分泌是其促进溃疡愈合的机制之一，而与抑制胃酸分泌无关。     

Helicobacter pylori infection delays the healing of acetic acid-induced gastric ulcer in Japanese monkeys

To clarify the relationship between Helicobacter pylori and the healing of gastric ulcers, we investigated the healing of acetic acid-induced gastric ulcers in the antral mucosa of Japanese monkeys (n=5) infected with H. pylori and in control monkeys without H. pylori infection (n=6). Using H. pylori-infected Japanese monkeys as an experimental model, gastric ulcers were induced endoscopically with acetic acid. Healing of ulcers and factors that influenced healing were studied. Continuous colonization with H. pylori was confirmed in the infected group throughout the observation period; no H. pylori were isolated from the gastric mucosa of the control group. White scarring was not observed in any infected monkeys 4 weeks after ulcer formation, but was observed in one (20%) of five monkeys at 6 weeks and in all five monkeys eight weeks after ulcer formation. In the control group, white scarring was observed in one (16.7%) of six monkeys at 4 weeks and in six monkeys at 6 (P< 0.01 vs infected group) and 8 weeks. The ammonia concentration of the gastric secretions and the grade of inflammation were significantly increased in the H. pylori-infected group compared with the control group (P< 0.01 and P< 0.001, respectively). The volume of intracellular PAS-positive substance was decreased (P< 0.025–0.01) at the ulcer margin in the infected group compared with the ulcer margin in the control group. The proliferation of gastric epithelial cells was markedly accelerated at the ulcer margin in the infected group compared with the ulcer margin in control group (P< 0.025–0.01). Our results strongly suggest that H. pylori infection delays the healing of gastric ulcers.     

苯妥英钠对大鼠实验性胃溃疡的保护作用

目的观察苯妥英钠对大鼠实验性胃溃疡的保护作用。方法采用水应激法、冰醋酸烧灼法建立大鼠动物实验两种溃疡模型随机分为苯妥英钠（PHT）大剂量组、小剂量组、雷尼替丁组和生理盐水组、连续给药14d，处死动物后观察实验结果。结果苯妥英钠大、小剂量组均显示出保护作用（P〈0.05），但大剂量组的保护作用不如小剂量组明显。结论苯妥英钠对大鼠实验性胃溃疡的胃黏膜有一定的保护作用，且保护作用与剂量成负相关，小剂量的保护作用要好干大剂量。     

Indomethacin treatment during initial period of acetic acid-induced rat gastric ulcer healing promotes persistent polymorphonuclear cell-infiltration and increases future ulcer recurrence

The study was performed to examine whether indomethacin administered during the initial period of acetic acid-induced gastric ulcer healing affects future ulcer recurrence. Gastric ulcers were produced in rats by subserosal injection of acetic acid. Indomethacin (1 mg/kg/day, orally) administered either alone or concomitant with ornoprostil (50µg/kg/day, orally) was started on the fourth day and continued for 56 days. In rats whose ulcer healed at the 90th day after production of ulcer, endoscopy was done every 30 days to examine recurrence of ulcer. Gastric specimens were obtained 10, 30, 60, 90, and 240 days after ulcer production for histology, to quantitate the height of regenerated mucosa, thickness of fibrous tissue, degree of polymorphonuclear cell infiltration, and PAS-positive cells. Cumulative ulcer recurrence rate was significantly higher in rats initially treated with indomethacin than in controls. Increased polymorphonuclear cell infiltration was the major histologic abnormality persisting after cessation of indomethacin. Ornoprostil reversed these abnormalities caused by indomethacin. In conclusion, the administration of indomethacin during the initial period of the ulcer healing promoted persistent polymorphonuclear cell infiltration and increased ulcer recurrence rates, possibly via a prostaglandin-dependent mechanism.The work was supported by The Ministry of Education, Science and Culture of Grant-in-Aid for General Scientific Research 02454236 and by the DVA Medical Research Service.     

血红蛋白氧化酶诱导剂Hemin在乙酸诱导大鼠胃溃疡中的作用

目的众多研究表明血红蛋白氧化酶(Heme Oxygenase,HO)具有内源性组织细胞保护作用,诱导HO表达能减轻和限制炎症引起的组织损伤.本研究目的旨在研究HO诱导剂Hemin在乙酸诱导大鼠胃溃疡模型中所起的作用及可能的机制.方法用RT-PCR,Western blotting分别检测乙酸诱导大鼠胃溃疡1,3,7 d后胃粘膜中两种诱导型酶,HO-1和一氧化氮合酶(inducible nitric oxide synthase,iNOS)的表达.以溃疡面积判断胃粘膜损伤程度,研究HO-1诱导剂Hemin对乙酸诱导胃溃疡形成过程中胃粘膜损伤的影响,同时研究Hemin对胃粘膜iNOS表达及活性的影响以探讨其可能的作用机制.结果乙酸诱导大鼠胃溃疡后,胃粘膜HO-1和iNOS表达明显增强.HO诱导剂Hemin能显著增强HO-1 mRNA和蛋白质表达,但溃疡面积反而增大,炎症加重.处理组大鼠溃疡面积1 d为(77±5)mm2,明显大于对照的(51±3)mm2(P＜0.01,n=10);3 d为(53±4)mm2,明显大于对照(36±3)mm2(P＜0.01,n=10).同时Hemin能显著增强胃粘膜iNOS的表达及iNOS的活性,溃疡诱导1 d Hemin组iNOS的活性为5.3±0.3,对照3.1±0.3(P＜0.01,n=10);3 d Hemin组5.7±0.5,对照3.8±0.4(P＜0.01,n=10,单位为pmol[3H]瓜氨酸·min-1·g蛋白-1).结论在乙酸诱导的胃溃疡模型中,HO-1表达增加对胃粘膜可能存在一定程度的保护作用,但这一保护作用不足于抵消其他损害因素如NO过度产生所导致的粘膜损伤.HO代谢产物可能尚具有双向作用,即生理性产生增加具有粘膜保护作用,过度产生可能存在细胞毒性作用.     

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.     

根除幽门螺杆菌对胃溃疡愈合质量及复发的影响研究

目的探讨幽门螺杆菌（Helicobacter pylori，Up）对胃溃疡愈合质量及复发的影响。方法120例坳阳性活动期胃溃疡患者，口服泮托拉唑、阿莫西林、甲硝唑一周后，继续口服泮托美拉唑5周。治疗结束后复查胃镜取病理组织学检查并检测Hp根除情况，对比却根除组与却根除失败组内镜下溃疡愈合形态差异和愈合质量（包括内镜下再生黏膜成熟度和再生黏膜组织学成熟度）。所有患者随诊1年以上了解溃疡复发情况。结果治疗后92例胃溃疡患者月p检测阴性，坳根除率为80．43％；却根除组与跏根除失败组在内镜下愈合率方面的差异无显著性意义（P〉0．05），但两组在再生黏膜成熟度和再生黏膜组织学成熟度方面的差异有显著性意义（P〈0．01）。坳根除组1年溃疡复发率为4．35％，却根除失败组为21．43％，两组差异有显著性意义（P〈0．05）。结论根除Hp可提高胃溃疡的愈合质量，减少溃疡病复发。     

Effects of Changtai granules, a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats

AIM: To study the effects of Changtai granules (CTG), a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats. METHODS: Healthy adult Sprague-Dawley (SD) rats of both sexes, weighing 250-300 g, were employed in the present study. The rat colitis models were induced by 2, 4,6-trinitrobenzene sulfonic acid (TNBS) enemas at a concentration of 100 mg/kg in 50% ethanol. The experimental animals were randomly divided into dexamethasone (DX) treatment, CTG treatment, and model control groups, which were intracolicly treated daily with DX (0.2 mg/kg), CTG at doses of 2.9, 5.7 and 11.4 g crude drug/kg, and the equal amount of saline respectively from 6 h following induction of the colitis in rats inflicted with TNBS to the end of study. A normal control group of rats treated without TNBS but saline enema was also included in the study. After 3 wk of treatment, the animals were assessed for colonal inflammatory and ulcerative responses with respect to mortality, frequency of diarrhea, histology and myeloperoxidase activity (MPO). RESULTS: The therapeutic effect of CTG on ulcerative colitis (UC) was better than DX. CTG effectively inhibited the activity of granulocytes, macrophages and monocytes in a dose-dependent manner. Also it reduced MPO and formation of inflammation in colonic mucosal tissue. Furthermore, administration of CTG significantly prevented body mass loss and death, and decreased frequency of diarrhea in UC rats, when compared with the model control group rats. CONCLUSION: CTG would prove to be an ideal drug for chronic UC, and is warranted to be studied further.     

Rebamipide,novel prostaglandin-inducer,accelerates healing and reduces relapse of acetic acid-induced rat gastric ulcer comparison with cimetidine

This study was done to elucidate whether rebamipide during the initial period of acetic acid-induced gastric ulcer affected healing and future ulcer relapse. The cumulative healing rate was higher in rats given rebamipide alone or those given rebamipide and cimetidine during and after administration, but not in rats given cimetidine alone, compared to control rats. Cumulative relapse rate was significantly lower in rats initially given rebamipide alone or those given rebamipide and cimetidine than in rats initially given cimetidine alone. These results suggest that rebamipide is beneficial for obtaining a better quality of ulcer healing and reduction of future ulcer relapse.     

Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats

AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol-induced gastric mucosal injuries in rats. METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gave GbE 8.75,17.5,26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers, gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured. RESULTS: The findings of our study are as follows: (1) GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH contents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanol produced an increase in JNK activity in gastric mucosa which also significantly inhibited by pretreatment with GbE; and (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated rats. CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of cell apoptosis.