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The Therapeutic Effect And Mechanism Of The Hydrotalcid On The Experimental Gastric Ulcer

Posted on:2016-03-28Degree:MasterType:Thesis
Country:ChinaCandidate:F ShenFull Text:PDF
GTID:2284330470957378Subject:Internal medicine
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Gastric ulcer is a common clinical disease, the pathogenesis of it was the imbalance between attack factor and defense factor of gastric mucosa. The constant recurrence of gastric ulcer was a worldwide public health problem. It is difficult to achieve perfect quality of gastric ulcer healing only by using proton pump inhibitors and eradicating helicobacter pylori. The ulcer recurrence rate was7.09%after treatment with proton pump inhibitors, and the ulcer recurrence of patients with helicobacter pylori infection was23.33%; the ulcer recurrence still as high as6.45%of patients with eradication of helicobacter pylori. The hydrotalcid which is one of the gastric mucosa protectant has been mainly used in the treatment of indigestion, heartburn in the past, but it was used to treat erosive esophagitis, gastric ulcer now because of the mucosal protective function. Originally the mechanism was considered to be neutralizing gastric acid, but recent studies have shown that the mechanism may be not so simple. In this study, we established the model of acetic acid-induced gastric mucosal lesion in rats. Then we observed the efficiacy of hydrotalcid with different doses in this model and measured indicators related QOUH. Material and methods1.Laboratory animals:64healthy, sexual-mature Wistar rats, female and male in a half, were adopted to the research.2.Acetic acid-induced ulcers:After fasting for24h, rats were narcotized. Then the stomach was removing and0.2mL acetic acid solution was injected into the submucosal layer at the region between the fondus and the pylorus on the anterior wall. Then the abdomen was closed. The concentrations of acetic acid solution were99.5%.3.Division:16rats were killed to confirm whether the acetic acid-induced gastric ulcer exist. The rest of48rats with acetic acid-induced gastric ulcers were divided into3groups. Saline group, low-dosage and high-dosage group of hydrotalcid, every16rats in each group. Saline group:the rats received intragastrically normal1mL saline twice daily for14days; low-dose hydrotalcid group:the rats received intragastrically hydrotalcid(880mg/kg/d) twice daily for14days; high-dose hydrotalcid group:the rats received intragastrically hydrotalcid(1230mg/kg/d) twice daily for14days.4.Methods:We observed the common clinical manifestation and mucosal mophology of the rats, measured and calculated the ulcer index and ulcer inhibition rate. Then the blood samples were obtained to measure the PGE2and EGF concentration, the gastric tissue samples were obtained to measure the hexosamine level. The rest of gastric ulcer samples were stained with HE, CD31, AB-PAS, VG. The thickness of mucosa, the number of cystically dilated glands, the MVD, the concentration of mucus, level of the hexosamine, the expression of PGE2, EGF and EGFR of each group were compared.Results1.General observation:Gastric ulcer in saline group were huge and with unclean surface; in low-dosage and high-dosage group of hydrotalcid were only a small amount of punctate erosions and mucosal hyperemia. The lower ulcer index(UI) and increased ulcer inhibition were observed in low-dosage and high-dosage group of hydrotalcid.2.The level of EGF and PGE2in Seru:Comparing to saline group[(12.2±2.2)pg/mL], the concentration of epidermal growth factor(EGF) in low dose hydrotalcid group[(16.3±1.8)pg/ml] and high dose hydrotalcid group [(15.8±2.8)pg/ml] were elevated(p<0.01). Comparing to saline group [(270.5±26.0) pg/ml], the concentration of prostaglandin E2(PGE2) in low dose hydrotalcid group[(308.9±32.7)pg/ml] and high dose hydrotalcid group [(310.0±30.1)pg/ml] were increased(p<0.01).3.The level of hexosamine in mucosal Surrounding ulcer:Comparing to saline group[(20.7±4.2)mg/g protein], the concentration of hexosamine in low dose hydrotalcid group[(33.2±6.6)mg/g protein] and high dose hydrotalcid group [(32.7±10.9)mg/g protein] were elevated(p<0.01).4.Pathologic specimens:In hydrotalcid groups, restored mucosa thickness increased, cystically dilated glands decreased, microvessel density(MVD) increased, the secretion of mucus and the concentration of hexosamine elevated, the expression of EGF, epithelial growth factor receptor(EGFR) and PGE2was increased.ConclusionHydrotalcid can obviously improve the ulcer regenerative mucosal histological and functional maturity, as well as the quality of ulcer healing (QOUH).
Keywords/Search Tags:experimental gastric ulcer, hydrotalcid, QOUH
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