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ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang (SHXXT) in protecting stress gastric ulcer (SGU) in rats through network pharmacology, molecular docking, and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Information Database (TCMID), Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM), and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), GeneCards database, and PharmGKB database. Herbal-ingredient-target (H-C-T) network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction (PPI) of drug and disease intersection targets was analyzed by using the Protein Interaction Platform (STRING) database. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery (DAVID). The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software, and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened, and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B (Akt), phosphatase and tensin homolog deleted on chromosome ten (PTEN), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and cyclooxygenase-2 (COX-2) are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group, the ulcer index (UI) of the model group was significantly increased (P<0.01), and the serum levels of TNF-α and IL-1β significantly increased (P<0.01). The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated (P<0.05). The phosphorylation levels of PI3K, Akt, and nuclear factor kappa-B (NF-κB) were significantly up-regulated (P<0.05). Compared with the model group, the UI of the treatment group was significantly reduced (P<0.01), and the serum levels of TNF-α and IL-1β were significantly reduced (P<0.01). The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated (P<0.01), and the phosphorylation levels of PI3K, Akt, and NF-κB were significantly downregulated (P<0.01). ConclusionThe application of network pharmacology prediction, molecular docking simulation, and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.
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OBJECTIVE@#To observe the effect of acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) on intestinal flora and Toll-like receptors-4 (TLR4) in brain and intestinal tissue in rats with stress gastric ulcer (SGU), and to explore the possible mechanism of acupuncture for SGU.@*METHODS@#Thirty-one male SD rats were randomly divided into a blank group (@*RESULTS@#Compared with the blank group, the gastric mucosal damage index was significantly increased in the model group (@*CONCLUSION@#Acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) could alleviate SGU in rats, and its mechanism may be related to increasing the diversity of intestinal flora, promoting the disorder of intestinal flora to normal, and reducing the overexpression of TLR4 in brain and intestinal tissues.
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Animais , Masculino , Ratos , Pontos de Acupuntura , Terapia por Acupuntura , Encéfalo , Microbioma Gastrointestinal , Ratos Sprague-Dawley , Úlcera Gástrica/terapia , Receptor 4 Toll-Like/genéticaRESUMO
OBJECTIVE@#To observe the effect of acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36) on intestinal flora in rats with stress gastric ulcer (SGU) , and to explore the mechanism of acupuncture promoting SGU recovery.@*METHODS@#Thirty-one SPF SD rats were randomly divided into a control group (7 rats), a model control group (8 rats), an acupuncture group (8 rats) and a medication group (8 rats). The rats in the model group, acupuncture group and medication group were selected to applied the improved restraint water-immersion stress method to establish the SGU model. After modeling, the rats in the control group and model group were fixed and restrained for 20 min every day for a total of 5 days; the rats in the acupuncture group were intervented with acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36), once a day, 20 min each time, and twisting needle for 30 s every 5 min for a total of 5 days; the rats in the medication group were gavaged by solution of omeprazole enteric-coated tablet (200 mg/mL), 2 mL for each rat, once a day. Guth method was used to calculate the gastric mucosal damage index (GMDI), HE staining was used to observe the pathological changes of gastric mucosa, and 16SrDNA identification was used to detect the structural abundance of intestinal flora.@*RESULTS@#Compared with the control group, the GMDI of rats in the model group was increased (<0.01), the gastric mucosal pathological changes were significant, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all decreased (<0.05), the diversity index Simpson was increased (<0.05). Compared with the model group, the GMDI of rats in the acupuncture group and medication group was reduced (<0.01, <0.05), the gastric mucosal damage degree was reduced, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all increased (<0.05) and the diversity index Simpson decreased (<0.05). Compared with the medication group, the GMDI of rats in the acupuncture group was reduced (<0.01), the recovery of gastric mucosal injury was better than that of the medication group.@*CONCLUSION@#Acupuncture can effectively improve gastric mucosal injury of SGU, and the mechanism may be related to increasing the diversity of intestinal flora and promoting the correction of the disordered intestinal flora.
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Animais , Ratos , Pontos de Acupuntura , Terapia por Acupuntura , Microbioma Gastrointestinal , Distribuição Aleatória , Ratos Sprague-Dawley , Úlcera Gástrica , Microbiologia , TerapêuticaRESUMO
The stress gastric ulcer is due to a stress-induced gastric erosions, superficial ulcers and bleeding gastric mucosal le-sions characterized by stress. Its etiology is closely associated with lives, the incidence is increasing. In recent years, the the basic re-search of drugs focuses on inhibition of oxidative damage caused by stress, anti-inflammatory cytokine expression, and regulation of gastric acid, etc., and made a lot of success. Treatment choice of stress ulcer drug gradually increased. The effects of plant extracts on stress ul-cer get more and more attention. This article reviews research progress of the treatment drugs of stress ulcer in the current stage.
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Objective To investigate the effect of electroacupuncture at point Zusanli (ST36) on gastric expression of heat shock protein 70 (HSP70) mRNA in rats with stress gastric ulcer and explore the molecular mechanism of its prevention and treatment of gastric ulcer. Method Fifty-one SD rats were randomly allocated to normal control (normal), stress gastric ulcer (model) and electroacupuncture at point Zusanli (electroacupuncture) groups. A model of stress gastric ulcer was made by cold restraint. From the second day after model making, the electroacupuncture group received electroacupuncture at point Zusanli 20 min once daily for three consecutive days, with left and right points Zusanli alternately needled; the model group, the same restraint treatment as in the electroacupuncture group; the normal group, no treatment. Gastric mucosal ulcer index (UI) was calculated using the GUTH’s method. The pathological morphology of gastric tissue was observed by HE staining. Gastric HSP70 mRNA expression was determined by RT-PCR. Result Different numbers and sizes of obvious gastric mucosal ulcers were observed, UI increased significantly (P<0.001) and HSP70 mRNA expression decreased significantly (P<0.05) in the model group compared with the normal group. The pathological change in gastric tissue improved somewhat, gastric mucosal UI decreased significantly (P<0.05) and HSP70 mRNA expression increased significantly (P<0.01) in the electroacupuncture group compared with the model group. Conclusion Electroacupuncture at point Zusanli can upregulate gastric HSP70 mRNA expression and promote the repair of gastric mucosa injuries in rats with stress gastric ulcer.