Ligustrazine alleviates gastric mucosal injury in a rat model of acute necrotizing pancreatitis

BACKGROUND: Acute necrotizing pancreatitis (ANP) leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant organ injury. The aim of this study was to explore the relationship between gastric microcirculatory impairment and inflammatory mediators released in rats and to evaluate the therapeutic effect of ligustrazine extracted from Rhizoma ligusticum wallichii on gastric mucosa injury in a rat model of ANP. METHODS: Ninety-six Sprague-Dawley rats were randomly divided into three groups: normal control (group Q; ANP without treatment (group P); and ANP treated with ligustrazine (group T). The ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 ml/kg). Group C was given isovolumetric injection of 9 g/L physiological saline by the same route. Group T was injected with ligustrazine (10 ml/kg) via the portal vein. The radioactive biomicrosphere technique was used to measure the blood flow 2 and 12 hours after the induction of ANP. Samples of the pancreas and stomach were taken to assess pathological changes by a validated histology score; meanwhile, the levels of serum interleukin-1 beta (IL-1 beta) were determined. Gastric tissues were also used to measure the level of myeloperoxidase (MPO), which is expressed intracellularly in the azurophilic granules of neutrophils. RESULTS: Blood flow in group P was significantly lower than that in group C (P < 0.01). Pathological changes were significantly aggravated in group P. The gastric MPO activity in group P was significantly higher than that in group C (P < 0.01). The level of serum IL-1 beta in group P increased more significantly than that in group C (P < 0.01). Blood flow of the stomach in group T was significantly higher than that in group P after 2 hours (P < 0.01). The pathological changes were significantly alleviated in group T. The MPO activity of group T was significantly lower than that of group P (P < 0.01). Although serum IL-1 beta level of group T, was higher than of group C (P < 0.01), it was lower than that of group P (P < 0.01). There was a negative correlation between gastric blood flow and MPO activity (r=-0.983, P < 0.01), and between gastric blood flow and pathological score (r=-0.917, P < 0.05). CONCLUSIONS: Decreased gastric blood flow and increased inflammatory mediators can be seen early in ANP, and both are important factors for gastric and mucosal injury. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the pancreas and stomach.

Effect of acupuncture at different meridian acupoints on changes of related factors for rabbit gastric mucosal injury

AIM： To explore the regularity of multi-meridians controlling a same viscus （MMCSV）. METHODS： The rabbit gastric ulcer model was established by ethanol intragastric instillation. Fifty-six rabbits were randomly divided into normal group, model group （MG）, model plus acupuncture at Foot Yangming Meridian group （YMG）, model plus acupuncture at Foot Taiyin Meridian group （TYG）, model plus acupuncture at Foot Shaoyang Meridian group （SYG）, model plus acupuncture at Foot Jueyin Meridian group （JYG）, model plus acupuncture at Foot Taiyang Meridian group （TYMG）, with eight rabbits in each group. Gastric mucosal nitric oxide （NO） and nitric oxide synthase （NOS） were assayed by the nitric acid reductase method, and prostaglandin E2 （PGE2） and epidermal growth factor （EGF） were measured by radioimmunoassay. The comprehensive effects were analyzed by weighing method. RESULTS： Compared to MG, SYG, JYG and TYMG, the rabbits gastric mucosal injury index （GMII） reduced very significantly in YMG （P〈0.01）. Compared to MG, the GMII also reduced significantly in TYG （P〈0.05）. NO, NOS, PGE2 and EGF increased very significantly in YMG （P〈0.01）. The EGF in YMG also increased significantly than that in TYG compared to those in MG, SYG, JYG and TYMG （P〈0.05）. The PGE2 and EGF also increased very significantly in TYG than those in MG, JYG and TYMG （P〈0.01）. While compared to SYG, the NOS increased significantly in TYG （P〈0.05）. NOS was the highest in YMG （P〈0.01）, and was higher in TYG than in MG （P〈0.01）. CONCLUSION： MMCSV is common. The Foot Yangming Meridian is most closely related to the stomach, followed by Foot Taiyin Meridian, Foot Shaoyang Meridian and Foot Jueyin Meridian. Foot Taiyang Meridian has no correlation with the stomach.

Hydrogen sulfide attenuates gastric mucosal injury induced by restraint water-immersion stress via activation of KATPchannel and NF-κB dependent pathway

AIMTo explore the effect of hydrogen sulfide (H2S) on restraint water-immersion stress (RWIS)-induced gastric lesions in rats and the influence of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway on such an effect.METHODSMale Wistar rats were randomly divided into a control group, a physiological saline (PS) group, a sodium hydrosulfide (NaHS) group, a glibenclamide (Gl) group, Gl plus NaHS group, a pyrrolidine dithiocarbamate (PDTC) group, and a PDTC plus NaHS group. Gastric mucosal injury was induced by RWIS for 3 h in rats, and gastric mucosal damage was analyzed after that. The PS, NaHS (100 μmol/kg body weight), Gl (100 μmol/kg body weight), Gl (100 μmol/kg or 150 μmol/kg body weight) plus NaHS (100 μmol/kg body weight), PDTC (100 μmol/kg body weight), and PDTC (100 μmol/kg body weight) plus NaHS (100 μmol/kg body weight) were respectively injected intravenously before RWIS.RESULTSRWIS induced serious gastric lesions in the rats in the PS pretreatment group. The pretreatment of NaHS (a H2S donor) significantly reduced the damage induced by RWIS. The gastric protective effect of the NaHS during RWIS was attenuated by PDTC, an NF-κB inhibitor, and also by glibenclamide, an ATP-sensitive potassium channel blocker, in a dose-dependent manner.CONCLUSIONThese results suggest that exogenous H2S plays a protective role against RWIS injury in rats, possibly through modulation of KATP channel opening and the NF-κB dependent pathway.

Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

AIM： To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica （Cactaceae） on the healing of ethanol-induced gastritis in rats. METHODS： Chronic gastric mucosa injury was treated with mucilage （5 mg/kg per day） after it was induced by ethanol. Lipid composition, activity of 5＇-nucleotidase （a membrane-associated ectoenzyme） and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS： Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine （PC） decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5＇-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION： The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine （PE）, may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

Protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats

Objective:To observe the protective effect of omeprazole on gastric mucosal of cirrhotic portal hypertension rats.Methods:All rats were randomly divided into normal control group,cirrhosis and treatment group.Thioacetamide was used to establish rat model of cirrhotic portal hypertension.The necrotic tissue of gastric mucosa ulcer focus,degree of neutrophils infiltration at the ulcer margin,portal pressure,portal venous flow,abdominal aortic pressure,abdominal aortic blood flow at front end,gastric mucosal blood flow（GMBF）,glycoprotein（GP）of gastric mucosa,basal acid secretion,H’ back-diffusion,gastric mucosal damage index,NO,prostaglandin E2（PGE2） and tumor necrosis factor-α（TNF-α） were determined respectively,and the pathological changes of gastric mucosa were also observed by microscope.Results:Compared with cirrhosis group and the control group,the ulcer bottom necrotic material,gastric neutrophil infiltration and UI of the treatment group were all decreased significantly（P【0.01）,GMBF value,GP values,serum NO,PGE2,TNF- a were all significantly increased.Conclusions:Omeprazole has an important protective effect on gastric mucosal and it can increase gastric mucosal blood flow and related to many factors.

Total triterpenes from fruits of Chaenomeles speciosa(Sweet) Nakai protect against indomethacin-induced gastric mucosal injury: involvement of TFF1-mediated EGF/EGFR and apoptotic pathways

OBJECTIVE Gastric ulcers affect people of all ages and half of the world's population,which is being considered as the new"plague of the 21st century".As is well known,gastric mucosa is known as the first guard to protect the stomach from ulcer injury,while the aetiology of gastric ulcer is relative to imbalances between gastric mucosal protective and aggressive factors.Therefore,reducing or eliminating the aggressive factors,returning to the balance of between mucosal protective and aggressive factors,and then restoring the normal functional of gastric mucosal barrier could be crucial for treating the gastric ulcer.The fruits of Chaenomeles speciosa(TCS),also known as"mugua",might be processed into edible and health care derived products,and used as a commonly used traditional medicine in China for thousands of years.In China folk,there is a saying that"apricot one benefit,pear two benefits,mgua hundred benefits",so it has a"hundred-benefit"fruit reputation.Tujia nationality inhabitants in Southwestern China should have rheumatic diseases and peptic ulcers for living in the damp environments and bingeing on spicy and pungent foods.For the exis⁃tence of the fruit derived products of Chaenomeles speciosa as their complementary foods or snacks,the habit makes them rarely suffer from the two kinds of diseases.Enlightened by these,we had investigated the structure-activity rela⁃tionships,screened out CSTT with gastroprotective activity.Our previous studies demonstrated that TCS owned effec⁃tively therapeutic effects on gastric ulcer patients and animals,and further confirmed that TFF1 and apoptotic pathway were closely interrelated with its exerting gastroprotection.However,its underlying molecular mechanisms involved have not been fully elucidated.The current study was to further investigate its protective effect on indomethacin(IND)-damaged RGM-1 cells and rats and its underlying mechanisms through modulating TFF1-mediated EGF/EGFR and apoptotic pathways.METHODS The gastroprotection of TCS was evaluated with IND-induced gastric lesions model in RGM-1 cells and rats.In vitro,the proliferation,migration,mitochondrial viability and apoptosis were assessed,In vivo,ulcer index,ulcer inhibition rate,gastric juice acidity,gastric wall mucus(GWM),histopathology of gastric mucosa were detected.The gastroprotective effects of TCS through the TFF1-mediated EGFR/EGFR and apoptotic pathways were presented and measured by qRT-PCR and Western blotting assays.RESULTS TCS had gastroprotective function,which was related to the amelioration in promoting IND-damaged RGM-1 cell proliferation and migration,hoisting gastric juice acidity and GWM,improving ulcer index and ulcer inhibition rate,attenuating the hemorrhage,edema,epithelial cell loss and inflammatory cell infiltration of gastric mucosa,upregulating proliferation cell nuclear antigen,Bcl-2,Bcl-xl mRNA and TFF1,EGF,p-EGFR,p-Src,pro-caspase-3,pro-caspase-9 protein expressions,mitochondrial viability,mitochondrial cytochrome C concentration and p-EGFR/EGFR,p-Src/Src,Bcl-2/Bax,Bcl-xl/Bad ratioes,downregulating Bax,Bad,Apaf-1 mRNA and cleaved-caspase-3,cleaved-caspase-9,cleaved-PARP-1 protein expressions,cytosol cytochrome C concentration.CONCLUSION TCS′s gastroprotective effect was closely connected with boosting TFF1 expression,acti⁃vating TFF1-mediated EGF/EGFR pathway,thus restraining mitochondrial-dependent apoptosis,which provided new insights into interpreting its underlying mechanism and promised to act as a candidate drug to treat gastric mucosal injury.

EFFECT OF ELECTROACUPUNCTURE OF "ZUSANLI" ON VIP CONTENTS OF THE PERIPHERAL BLOOD, GASTRIC MUCOSAL AND BRAIN TISSUES IN GASTRIC MUCOSAL INJURY RATS

Objective: To observe the therapeutic effect of electroacupuncture (EA) of "Zusanli"(ST 36) on vasoactive intestinal peptide (VIP) levels in the peripheral blood, gastric mucosal and brain tissues in experimental gastric injury rats. Methods: Gastric mucosal injury model was established by using cold restraining stress method. 40 Wistar rats were randomly and evenly divided into normal control group, model group, EA group and non acupoint group. VIP contents of plasma and gastric mucosal and medulla oblongata tissues were assayed using radioimmunoassay and gastric mucosal blood flow (GMBF) was measured by employing hydrogen clearing method. Results: In cold restraining stress rats, spot and strip like bleeding necrosis foci in the gastric mucous primarily in the gastric antrum could be seen clearly, GMBF and VIP contents in plasma, gastric mucous and brain tissues declined significantly (P<0.05, 0.01), while the gastric mucosal lesion index (LI) raised significantly (P<0.05) in comparison with those of normal control group. Following EA of "Zusanli" (ST 36), GMBF decreased pronouncedly, VIP contents of the plasma, bulba and gastric mucosal tissues increased strikingly in comparison with model group (P<0.01). Conclusion: EA of "Zusanli" (ST 36) possesses a protection effect on gastric mucous under stress condition and VIP is involved in the effect of EA.

Protective role of fruits of Rosa odorata var. gigantea against WIRSinduced gastric mucosal injury in rats by modulating pathway related to inflammation, oxidative stress and apoptosis

Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea(FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress(WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved.Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin(H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot.Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase(GSH-PX), superoxide dismutase(SOD) and catalase(CAT) contents;anti-inflammatory cytokines interleukin-10(IL-10) and prostaglandin E2(PGE2) levels as well as regulatory factors tumor necrosis factor-a(TGF-a) and somatostatin(SS) contents, while decreasing malondialdehyde(MDA), nitric oxide synthase(i NOS), tumor necrosis factor(TNF-a), interleukin-1β(IL-1β), interleukin-6(IL-6), gastrin(GAS)and endothelin(ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen(PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-ΚB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival.Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis systems.

Study of Clinical and Genetic Risk Factors for Aspirin-inducec Gastric Mucosal Injury

Background： Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions. Methods： We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated. Results： Among 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history （odds ratio [OR] = 5.924, 95% confidence intervals [C/]： 2.115-16.592）, dual anti-platelet medication （OR = 3.443, 95% CI： 1.154-10.271 ）, current Helicobacterpylori infection （OR = 2.242, 95% CI： 1.032-4.870）, male gender （OR = 2.211, 95% CI： 1.027-4.760）, GG genotype ofrs2243086 （OR = 4.516, 95% CI： I. 180-17.278）, and AA genotype ofrs 1330344 （OR = 2.178, 95% CI： 1.016-4.669） were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype ofrs2238631 and TT genotype ofrs2243100 was higher than in those without upper gastrointestinal bleeding. Conclusions： Peptic ulcer history, dual anti-platelet medication, tt. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs 1330344 were possible genetic risk factors. TT genotype ofrs2238631 and TT genotype ofrs2243100 may be risk factors for upper gastrointestinal bleeding in aspirin users.

Effect of Weikang Capsule(胃康胶囊)on Aspirin-Related Gastric and Small Intestinal Mucosal Injury

Objective To investigate the effects of Weikang Capsule(胃康胶囊,WKC)on aspirin-related gastric and small intestinal mucosal injury by magnetically controlled capsule endoscopy(MCCE).Methods Patients taking enteric-coated aspirin aged 40-75 years were enrolled in Beijing Anzhen Hospital,Capital Medical University from January 2019 to December 2019.The patients continued taking aspirin Tablet(100 mg per day)and underwent MCCE before and after 1-month combined treatment with WKC(0.9 g per time orally,3 times per day).The gastrointestinal symptom score,gastric Lanza score,the duodenal,jejunal and ileal mucosal injury scores were used to evaluate the gastrointestinal injury before and after treatment.Adverse events including nausea,vomiting,abdominal pain,abdominal distension,abdominal discomfort,dizziness,or headache during MCCE and combined treatment were observed and recorded.Results Twenty-two patients(male/female,13/9)taking enteric-coated aspirin aged 59.5±11.3 years with a duration of aspirin use of 28.0(1.0,48.0)months were recruited.Compared with pre-treatment,the gastrointestinal symptom rating scale scores,gastric Lanza scores,and duodenal mucosal injury scores were significantly reduced after 1-month WKC treatment(P<0.05),and jejunal and ileal mucosal injury scores showed no obvious change.No adverse events occurred during the trial.Conclusions WKC can alleviate gastrointestinal symptoms,as well as gastric and duodenal mucosal injuries,in patients taking enteric-coated aspirin;it does not aggravate jejunal or ileal mucosal injury,which may be an effective alternative for these patients(Clinical trial registry No.ChiCTR1900025451).