Protective role of nitric oxide in indomethacin-induced gastric ulceration by a mechanism independent of gastric acid secretion.

Gastric ulceration was induced in rats by i.p. injection of the non-steroidal anti-inflammatory drug (NSAID), indomethacin (IND) (30 mg kg(-1)). Pyloric ligation was carried out in each animal before injection to enable collection of the gastric juice. Three hours later, the animals were killed and their stomachs were removed. In the gastric juice, the amounts of mucin, pepsin and HCl were assessed. Gastric mucosa were scrapped for the determination of nitric oxide (NO) (as nitrite) after evaluation of the gastric ulcer index. The influence of arginine (ARG) (300 mg kg(-1)), a NO precursor, N(G)-nitro- l -arginine methyl ester (l -NAME) (50 mg kg(-1)), a non-selective constitutive nitric oxide synthase/inducible nitric oxide synthase (cNOS/iNOS) inhibitor, and the selective iNOS inhibitor aminoguanidine (AMG) (50 mg kg(-1)) were studied. Each NO modulator was injected i.p. 30 min before IND administration. Results indicated that IND elevated gastric acidity by 80% of the normal group, decreased non-significantly mucosal nitrite by 22% and exhibited a remarkably high ulcer index (chi = 17). Neither mucin nor pepsin levels were significantly altered. In comparison with the IND group, pretreatment with l -NAME caused a significant decrease in gastric HCl, further decrease in mucosal nitrite (50% of normal) and a two-fold increase in the ulcer index score (chi = 34), despite the decrease in HCl. AMG did not alter gastric acidity, decreased mucosal nitrite by 38% of the normal value and failed to alter significantly the ulcer index of IND. On the other hand, pretreatment with ARG did not alter the gastric acidity and raised mucosal nitrite by 10% above normal. Surprisingly, ARG improved the gastric ulcer score (chi = 1) almost similar to the normal score (chi = zero). Therefore, this study creates a new pathway for the potential treatment of NSAID gastric ulceration through modulation of NO synthesis, regardless of the effect on gastric acidity.     

Effect of SR 58611A,a beta-3 receptor agonist,against experimental gastro-duodenal ulcers

The present study was designed to study the effect of SR 58611A, a selective beta 3-adrenoceptor agonist against gastric ulcers: pylorus ligation, water immersion plus restraint stress (WIRS), ethanol, aspirin-induced and on cysteamine-induced duodenal ulcers, in rats. SR 58611A (10 mg/kg, p.o.) was found to be effective in attenuating gastric ulceration and the results were comparable with those from standard cimetidine-treated group. Apart from reducing ulcer index, SR 58611A significantly decreased total acidity and thereby exhibited antisecretory activity in pylorus ligation model. SR 58611A showed significant reduction in ulcer index alongwith significant rise in the gastric wall mucus content in WIRS model. Further it showed significant cytoprotective activity against ethanol insult, that was evident from significant reduction in ulcer index. It showed significant reduction in gastric ulceration in aspirin-treated rats. The drug was found to be ineffective in inhibiting the cysteamine-induced duodenal ulcers as evident from the ulcer index and total lesion area parameters. It is concluded that SR 586111A possesses significant gastroprotective activity. This activity could be attributed to the inhibition of gastric acidity, increase in gastric wall mucus content and the reversal of gastric microvascular injury resulting into protection of the vascular integrity.     

Gastroprotective Effect of Oxalis corniculata (Whole Plant) on Experimentally Induced Gastric Ulceration in Wistar Rats

The objective of the present study was to investigate the antiulcer activity of methanol extract of Oxalis corniculata (whole plant) using pylorus ligation and indomethacin-induced gastric ulceration in Wistar rats. The extract was preliminary evaluated for acute oral toxicity test using Organisation for Economic Co-operation and Development guidelines 423. Further, it was studied for antiulcer potential at the dose levels of 125, 250 and 500 mg/kg. Ranitidine was used as a standard drug (100 mg/kg). Acid secretory parameters like gastric volume, pH, total acidity and free acidity were measured in pylorus ligation model, whereas numbers of ulcers, ulcers score and ulcer index was measured in pylorus ligated and indomethacin treated rats. Pretreatment of test extract significantly (p<0.05) decreased the gastric volume, total acidity, free acidity and increase in the pH of the gastric fluid in pylorus-ligated rats. It also showed significant (p<0.05) decrease in number of ulcers, ulcers score and ulcer index in pylorus ligated and indomethacin treated rats. Results of the study suggest that, the methanol extract of Oxalis corniculata possesses significant antisecretory and antiulcer effects and justify the traditional usage of this herb to treat peptic ulcers.     

Comparative study of proton pump inhibitors on dexamethasone plus pylorus ligation induced ulcer model in rats

The present study was designed to compare ulcer protective effect of proton pump inhibitors viz. omeprazole, rabeprazole and lansoprazole against dexamethasone plus pylorus ligation induced ulcer model. Dexamethasone (5 mg/kg) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all the rats 15 min after the pylorus ligation. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 min prior to ligation was used for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as ulcer index, free and total acidity, gastric pH, mucin, pepsin and total proteins. Oral administration of proton pump inhibitors showed significant reduction in gastric acid secretion and ulcer protective activity against dexamethasone plus pylorus ligation induced ulcer model. The % protection of omeprazole, rabeprazole and lansoprazole was 84.04, 89.36 and 79.78, respectively. Rabeprazole significantly inhibited the acid-pepsin secretion and increased the gastric mucin secretion. The observations made in the present study suggest that rabeprazole is the most effective gastric antisecretory and ulcer healing agent as compared to omeprazole and lansoprazole.     

姜辣素对动物实验性胃溃疡的影响

目的考察姜辣素抗小鼠胃溃疡作用并初步探讨其作用机制。方法采用幽门结扎法致小鼠胃溃疡模型和阿司匹林致胃溃疡模型,判定胃黏膜损伤指数;收集胃液,测其胃液量,总酸度,胃蛋白酶活性及游离黏液量,胃壁结合黏液量及6-酮前列腺素F1α(6-keto-prostaglandin F1α,6-keto-PGF1α)的含量。结果姜辣素能减少幽门结扎和阿司匹林致胃黏膜损伤指数,对胃液分泌有抑制作用,可以显著降低胃液总酸度。但对胃蛋白酶无显著影响。对胃液中游离黏液和胃壁结合黏液的分泌有显著地促进作用。并能显著增加6-keto-PGF1α的含量。结论姜辣素具有一定的抗胃溃疡的作用,其机制可能与增加前列腺素E2(prostaglandin E2,PGE2)合成有关。     

Protection against gastric ulcer by verapamil

The effect of verapamil, a calcium channel blocker, was studied against stress (cold restraint), aspirin and pylorus ligation induced gastric ulcers in rats. Verapamil inhibited ulcerogenic response and ulcer index in all the three types of ulcers. Verapamil also decreased total and free gastric acidity without changing gastric secretory volume.     

胃散对胃溃疡模型大鼠胃黏膜保护作用的研究

目的 研究胃散对胃溃疡大鼠胃黏膜的保护作用。方法 采用乙酸烧灼型胃溃疡模型、幽门结扎型胃溃疡模型、乙醇损伤型胃溃疡模型,检测溃疡指数、胃酸总酸度、胃酸分泌速度和胃蛋白酶活性,综合考察胃散对胃溃疡模型大鼠胃黏膜的保护作用。结果 胃散在1、0.5、0.25 g/kg剂量下,对乙酸烧灼型胃溃疡有非常显著的促愈合作用;对幽门结扎型胃溃疡的形成有显著的抑制作用;对乙醇损伤的胃黏膜也有显著的保护作用;对胃液总酸度、胃酸分泌速度和胃蛋白酶活性有明显抑制作用,显著增加胃液分泌量。结论 胃散具有增加胃液分泌、抑制胃酸分泌、抑制胃蛋白酶活性、保护胃黏膜和防止胃溃疡的作用。     

The ulcer healing effect of protamine sulphate in rat stomach

BACKGROUND: Protamine sulphate has been reported to stimulate nitric oxide production from blood vessels, which is a pivotal factor for gastric ulcer healing. Our preliminary study also showed that protamine sulphate potentiated the ulcer healing effect of heparin. METHODS: Male SD rats with acetic acid-induced gastric ulcers were given protamine sulphate (40-80 mg/kg, s.c.) twice daily for 4 or 7 days. L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), an inhibitor of nitric oxide synthase (NOS), was given s.c. prior to protamine sulphate (80 mg/kg) treatment. Ulcer healing, angiogenesis, mucosal histological changes, NOS activity and growth factors were determined. RESULTS: Protamine sulphate dose-dependently accelerated gastric ulcer healing, which was accompanied by a significant increase in angiogenesis, mucosal regeneration and constitutive NOS activity. Inhibition of gastric secretion was observed. Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), tumour necrosis factor-alpha (TNF-alpha) or inducible NOS activity was also affected. L-NAME completely blocked the beneficial effects of protamine sulphate. CONCLUSIONS: Protamine sulphate accelerates gastric ulcer healing through a mucosal nitric oxide-dependent and possibly also the EGF-and bFGF-associated pathways, which are followed by an increase of angiogenesis and mucosal regeneration. Acid inhibition contributes in part to the ulcer healing action of protamine sulphate.     

Effect of hyperprolactinaemia as induced by pituitary homografts under kidney capsule on gastric and duodenal ulcers in rats.

The effect of hyperprolactinaemia, induced by two or four pituitary homografts under the kidney capsule, on gastric and duodenal ulcers has been studied. The acute gastric ulcer models used were pylorus ligation, indometacin-induced and ethanol-induced gastric ulcers. Chronic gastric ulcers were induced using acetic acid and duodenal ulcers by mercaptamine hydrochloride. After pylorus ligation, there was an approximate 30-40% increase in gastric secretion, a significant increase in total acidity (P < 0.01) and in the ulcer index (P < 0.01) in rats bearing pituitary homografts under the kidney capsule when compared with the sham-operated control. Hyperprolactinaemia did not affect the formation of ethanol-induced gastric ulcers but showed a 40% reduction in the development of indometacin-induced gastric ulcers. It also produced a 20% increase in the ulcer index in acetic acid-induced chronic gastric ulcers and a 30% increase in ulcer area in mercaptamine-induced duodenal ulcers. Our results showed that hyperprolactinaemia induced gastric acid secretion and thereby aggravated gastric and duodenal ulcers in rats. Hyperprolactinaemia did not affect gastric cytoprotection.     

The effects of verapamil on stress- and histamine-induced gastric lesions in rats

The influence of verapamil on stress-induced and histamine-induced gastric ulcers was investigated in rats. The influence of verapamil was also examined on various biochemical parameters that affect the development of these ulcer models. The animals were pretreated with intraperitoneal verapamil (1, 5, 25 mg/kg) by injection 1 h before the induction of experimental ulceration. The gastric lesions were induced by cold-restraint stress or intraperitoneal injection of histamine (300 mg/kg). The gastroprotective effects of verapamil were evaluated by determining the ulcer index, gastric mucus content, free and total acidity, lipid peroxidation and non-protein sulfhydryl content. Verapamil pretreatment at a dose of 25 mg/kg significantly reduced stress-induced ulcers. Verapamil enhanced mucus secretion, reduced total acidity and lipid peroxidation and decreased non-protein sulfhydryl content in a dose-dependent fashion. On the other hand, pretreatment with verapamil at any dose had no significant effect on histamine-induced ulcers. L-Arginine (L-A) (100 mg/kg) or L-nitroarginine (L-NNA) (100 mg/kg) were also injected i.p. to the animals 1 h before stress to test the role of nitric oxide (NO) in the mechanism of the gastroprotective activity of verapamil (25 mg/kg). The results suggested that verapamil stimulates gastric NO production, but the overproduction of NO worsens gastric ulcers. The effects of verapamil on experimentally induced ulcers may be related to its ability to induce biochemical alterations in the parameters measured in gastric tissue.     

Protective effect of leaves of Raphinus sativus Linn on experimentally induced gastric ulcers in rats

Raphinus sativus Linn (Cruciferae) commonly known as ‘Radish’ is a multipurpose herb cultivated in different parts of the world for its edible roots and leaves. The present study was aimed to evaluate the antiulcer activity of leaf extracts of R. sativus Linn on acetic acid induced chronic gastric ulcer and pylorus ligation induced gastric ulcer in rats. The acute oral toxicity study revealed that all the extracts were safe up to 2000 mg/kg per oral dose; hence one-tenth of this dose was selected for evaluation of antiulcer activity. In acetic acid induced gastric ulcer models, the ERS, CRS, EARS and AQRS have offered significant protection against acetic acid induced ulcers when compared to control group. While in pylorus ligation induced ulcer model the ERS, EARS and AQRS showed significant protection by decreasing the ulcer index, total acidity and free acidity. In conclusion the leaf extracts of R. sativus Linn are found to possess antiulcer property in the experimental animal models of gastric ulcers, which is consistent with the literature report in the folk medicine.     

Nitric oxide-mediated anxiolytic-like and antidepressant-like effects in animal models of anxiety and depression

The effects of microinjection of the nitric oxide (NO) precursor l-arginine (l-Arg), the NO synthase (NOS) inhibitors N-methyl-l-arginine (l-NAME) and 7-nitroindazole (7-NI), and the cyclic guanosine 3',5'-monophosphate (cGMP) analog 8-Br-cGMP into the dorsal raphe nucleus (DRN) were assessed in rats using the elevated plus maze (EPM) and the forced swim test (FST). l-Arg (100 and 200 nmol) produced an anxiolytic-like effect in the EPM. 8-Br-cGMP (25 and 50 nmol) dose-dependently increased locomotor activity. In the FST, antidepressant-like effects were produced by l-Arg (50 and 100 nmol) and 8-Br-cGMP (12.5 and 25 nmol). Dual effects were observed with NOS inhibitors l-NAME and 7-NI in both the EPM and FST. While low doses of l-NAME (25 nmol) or 7-NI (1 nmol) induced a selective increase in EPM open arm exploration and a decrease in immobility time in the FST, high doses (l-NAME 400 nmol, 7-NI 10 nmol) decreased locomotor activity. These results show that interference with NO-mediated neurotransmission in the DRN induced significant and complex motor and emotional effects. Further studies are needed to elucidate the mechanisms involved in these effects.     

Anti-ulcer actions of phytosphingosine hydrochloride in different experimental rat ulcer models

The gastroprotective activity of phytosphingosine hydrochloride (PS-HCl, CAS 554-62-1) was assessed in four different rat models of experimentally induced gastric ulcer. Various doses (2.5-10 mg/kg) of PS-HCI were orally administered to rats 30 min before the treatment with HCl/ethanol, indometacin, cysteamine, or to rats with ligated pylorus. Oral administration of PS-HCl (2.5-10 mg/kg) to rats prevented the acute ulcer formation in 4 different types of ulcer in a dose-dependent manner as follows: (1) HCl/ethanol-induced gastric mucosal membrane lesions (20.1-47.8% inhibition), (2) indometacin-induced gastric mucosal membrane lesions (4.6-31.9% inhibition), (3) duodenal ulcer induced by cysteamine (10-20% inhibition), (4) gastric secretion and ulceration following pylorus ligation (33.3-61.9% inhibition). These results indicate that PS-HCI may be useful for the prevention of gastric ulcer.     

L-arginine protects against stress-induced gastric mucosal lesions by preserving gastric mucus

1. We have shown that exogenously administered L-arginine protects against water immersion restraint (WIR) stress-induced gastric mucosal lesions in rats through preservation of nitric oxide (NO) generation via constitutive nitric oxide synthase (cNOS), but not inducible nitric oxide synthase (iNOS), in the gastric mucosa. We have also indicated that impaired gastric mucus synthesis and secretion occur through a decrease in gastric cNOS activity in WIR-stressed rats. Therefore, in the presesnt study, we examined whether exogenously administered L-arginine exerts a protective effect against WIR stress-induced gastric mucosal lesions in rats through preservation of gastric mucus synthesis and secretion by NO generated from the administered amino acid via cNOS in the gastric mucosa. 2. Rats were subjected to WIR stress for 3 and 6 h. Either L-arginine (150-600 mg/kg) or D-arginine (600 mg/kg) was injected intraperitoneally 0.5 h prior to WIR stress. Either N(G)-monomethyl L-arginine (L-NMMA; 100 mg/kg) or N(G)-monomethyl D-arginine (D-NMMA; 100 mg/kg) was injected subcutaneously 0.5 h prior to WIR stress. Total NOS, cNOS, iNOS, nitrite and nitrate (breakdown products of NO), hexosamine (an index of gastric mucin) and adherent mucus were assayed in the gastric mucosa. 3. Pretreatment with L-arginine, but not D-arginine, protected against gastric mucosal lesions in rats subjected to WIR stress for 3 and 6 h in a dose-dependent manner. Pretreatment with L-arginine, but not D-arginine, attenuated decreases in hexosamine and adherent mucus concentrations and cNOS activity and increases in total NOS and iNOS activities and nitrite/nitrate concentration in the gastric mucosal tissue of rats subjected to WIR stress for 3 and 6 h in a dose-dependent manner. Both the protective effect of L-arginine against gastric mucosal lesions and the attenuating effect of the amino acid on the decreases in gastric mucosal hexosamine and adherent mucus concentrations and cNOS activity in rats subjected to WIR stress for 6 h were counteracted by cotreatment with L-NMMA, a nitric oxide synthase inhibitor, but not D-NMMA. 4. These results suggest that exogenously administered L-arginine exerts a protective effect against stress-induced gastric mucosal lesions in rats at least partly through preservation of gastric mucus synthesis and secretion by NO produced from the administered amino acid via cNOS in gastric mucosal tissue.     

Antiulcer Activity of Ficus glomerata.

Abstract

The ethanol extracts of F. glomerata. Linn. (Moraceae) bark and leaves were studied for antiulcer activity against aspirin plus pylorus ligation–induced gastric ulcer, HCl-ethanol–induced ulcer, and water immersion stress–induced ulcer in rats. These plant extracts attenuated the gastric volume, free acidity, total acidity, and ulcer index. They also reduced the gastric lesion induced by HCl-ethanol mixture and showed protection against water immersion stress–induced ulcers.     

Inhibitory effects of Centella asiatica water extract and asiaticoside on inducible nitric oxide synthase during gastric ulcer healing in rats

In this study, the effects of Centella asiatica water extract (CE) and its active constituent, asiaticoside (AC), on the expression and activity of inducible nitric oxide synthase (iNOS) during gastric ulcer healing in rats were investigated. CE was prepared from Centella asiatica dry plant and the concentration of AC in CE was quantitatively determined with the use of high performance liquid chromatography analysis. Different concentrations of CE (0.10 g/kg and 0.25 g/kg) and AC (5 mg/kg and 10 mg/kg) were orally administered to rats with acetic acid-induced gastric ulcers. They were found to reduce the size of the ulcers at days 1, 3 and 7 after ulcer induction in a dose-dependent manner, with a concomitant attenuation of iNOS activity and protein expression at the ulcer tissues. The levels of nitrite and nitrate (NO(X)-), the stable end-products of nitric oxide (NO), in the gastric ulcer tissues were also decreased. N-[3-(aminomethyl)benzyl]acetamidine (1400W), a highly selective inhibitor of iNOS, was found to produce similar but more potent inhibition on iNOS activity at a dose of 0.1 mg/kg. These findings indicate that CE and AC have an anti-inflammatory property that is brought about by inhibition of NO synthesis and thus facilitates ulcer healing.     

Role of Blepharis maderaspatensis and Ammannia baccifera plant extracts on in vitro oxygen radical scavenging, secretion of gastric fluid and gastroprotection on ulcer induced rats

Context: Blepharis maderaspatensis L. Roth (BM) (Acanthaceae) and Ammannia baccifera L. (AB) (Lythraceae) are used in folk medicine for various stomach disorders. Objective: The chloroform and ethanol extracts of both plants were evaluated for antioxidant, gastric antisecretory, and gastroprotective properties. Methods: Antioxidant properties of the extracts were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and nitric oxide (NO) scavenging assay. The gastric antisecretory properties of the extracts were assessed, at a dose of 100 and 200 mg/kg, using aspirin-pylorus ligation induced gastric ulcer models and the gastroprotective activity of the extracts was assessed, at a dose of 100 and 200 mg/kg, using HCl-ethanol induced ulcer models in rats. Results and discussion: Ethanol extract of BM (EBM) possessed good antioxidant property with IC(50) values of 37.4 and 44.1 μg/mL in DPPH and NO scavenging assays respectively, where 25-250 μg/mL concentration in DPPH assay and 30-300 μg/mL concentration in NO scavenging assay were used. Ethanol extract of AB (EAB) at a dose of 200 mg/kg reduced the free acidity to 142.66 mEq/L and total acidity to 451.22 mEq/l. It reduced the gastric secretion with increase in pH from 2.2 to 3.15. Possessing good antisecretory activity, it also reduced the ulcer by 92.2% in aspirin and pylorus ligation induced gastric ulcer models. EAB increased the mucus secretion and adherent mucus in the tissues with a 71.43% reduction of ulcerin HCl-ethanol induced ulcer models, at a dose of 200 mg/kg. This activity can be attributed to the various flavonoids like rutin and kaempferol-3-O-β-glucopyranoside, and the phytosterol, β-sitosterol-3-O-β-glucopyranoside, and phenolics present in the extracts. Conclusion: EBM possessed significant antioxidant property while EAB possessed good antisecretory and gastroprotective activity.     

Antiulcer activity of ethanol leaf extract of Cassia fistula

The ethanol leaf extract (ELE) of Cassia fistula Linn. (Caesalpinaceae) was evaluated for antiulcer activity against pylorus ligation-induced gastric ulcer. Ranitidine (30?mg/kg b.w.) and ELE at doses of 250, 500, and 750?mg/kg b.w. were administered orally in different groups of rats (n = 6), 1?h prior to pyloric ligation. Four hours after pyloric ligation, the gastric juice was collected for evaluation of various parameters. The antiulcer activity of ELE was evidenced by the significant attenuation of gastric volume, pH, free acidity, and total acidity in the gastric juice of pyloric-ligated rats in a dose-dependent manner, and this protective effect could be due to strengthening of the mucosal defense mechanism. ELE pre-treatment significantly attenuated the fall in status of sialic acid and fucose accompanied by an increase in hexose, hexosamine, total non-amino polysaccharide, total carbohydrate, and C:P ratio in the gastric juice of pylorus-ligated rats, and this effect could be due to protection of the mucosal barrier system. ELE pre-treatment significantly prevented the increase in LPO and SOD accompanied by a fall in CAT, in the gastric juice of pyloric-ligated rats. This protective ability of ELE against pylorus ligation-induced gastric ulcer could be attributed to its free radical scavenging and antioxidant properties. Higher doses of ELE (750?mg/kg b.w.) produced maximum antiulcer activity comparable to ranitidine treatment. In essence, the antiulcer activity of ELE could be attributed to (i) a decrease in gastric acid secretion, (ii) protection of the mucosal barrier and restoration of mucosal secretions, (iii) inhibition of free radical generation or prevention of lipid peroxidation, and (iv) free radical scavenging or antioxidant properties.     

Evaluation of the effects of nicorandil on experimentally induced gastric ulcers

The present study was designed to evaluate the effects of a potassium channel opener, nicorandil, and to elucidate its possible mechanism of action in aspirin plus pylorus ligation induced and ethanol-induced gastric ulcers in rats. In an attempt to ascertain the involvement of K(ATP) channels in the modulation of gastric ulcers, the effects of nicorandil alone as well as in the presence of the K(ATP) channel blocker glibenclamide were studied. Nicorandil and glibenclamide were administered orally at a dose of 2 mg/kg throughout the study. Nicorandil showed significant protection in all the selected models that was evident from a significant reduction in the ulcer index. The results of nicorandil treatment were comparable with those of cimetidine treatment in both models. Glibenclamide was found to inhibit this effect of nicorandil. Further, glibenclamide showed proulcerogenic potential in ethanol and aspirin plus pylorus ligation models. In the aspirin plus pylorus ligation model, nicorandil showed a significant reduction in total acidity, pepsin activity, and protein content and a significant rise in mucin activity. The effect of nicorandil was also studied on gastric mucosal blood flow (GMBF). The GMBF was found to be more increased in the test group than in the control group, indicating enhancement of GMBF by nicorandil. Glibenclamide reversed this effect of nicorandil as well. It is concluded from our study that nicorandil possesses antiulcer activity in the models employed in the present study. This may be attributed to the opening of K(ATP) channels, inhibition of acid secretion, enhancement of mucin activity, and improvement in GMBF.     

秋茄提取物抗大鼠实验性胃溃疡作用研究

目的探讨海洋红树林植物秋茄枝水提取物活性部分B部位(fraction B of stem aqueous extracts of kandelia candel,SAEKC)对实验性大鼠胃溃疡的作用及其作用机制。方法将大鼠随机分为正常对照组、模型对照组、给药组(480、240、60mg·kg-13个剂量组)和西咪替丁组。各组每天灌胃给药(赋形剂,SAEKCB和西咪替丁),连续3d。除正常对照组外,其余各组大鼠在最后一次给药后通过水应激18h建立水浸束缚应激型胃溃疡大鼠模型,测定溃疡指数(UI),计算溃疡抑制率;同时建立幽门结扎型胃溃疡大鼠模型,造模后17h测定溃疡指数,计算溃疡抑制率,检测胃液量、胃蛋白酶活性,血清和胃组织一氧化氮(NO)含量。结果SAEKCB的高、中、低3个剂量组能明显减轻应激型胃溃疡大鼠胃黏膜损伤的程度(P<0.01,P<0.01,0<0.05),溃疡抑制率分别为模型对照组的0.411、0.404、0.254;SAEKCB能明显减轻幽门结扎型胃溃疡大鼠胃黏膜损伤的程度(P均<0.01),溃疡抑制率分别为模型对照组的0.556、0.361、0.306。480、240mg·kg-1剂量组能明显降低胃蛋白酶活性和胃液量(P<0.01或P<0.05)。给药3个剂量组均能提高胃组织NO含量,其中240、60mg·kg-1剂量组能明显升高血清NO含量(P均<0.01)。结论SAEKCB有明显抗应激型和幽门结扎型大鼠胃溃疡的作用,其效应呈剂量依赖性。对于幽门结扎型大鼠其机制可能在于减少胃液分泌、降低胃蛋白酶活性、提高血清和胃组织中NO水平。