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Effects Of Melatonin On Water-immersion And Restraint Stress-induced Gastric Mucosal Injury And Expression Of MMPs In Rats

Posted on:2016-05-23Degree:MasterType:Thesis
Country:ChinaCandidate:H Z GuiFull Text:PDF
GTID:2284330482971452Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Stress ulcer(SU) is a serious complication with acute gastric mucosal erosion, ulcer and bleeding under stress such as body’s serious trauma, severe disease and serious psychological disorders. The mechanism of SU has not yet fully understood, to prevent and cure still exist many disputes. The prevention and treatment of the SU mainly include: actively treating the primary disease and symptomatic treatment, early enteral nutrition support and gastrointestinal decompression, and actively using acid suppression drugs and gastric mucosa protectant. There are two sections in this study.Section one: Influence of non-fasting and fasting treatments on water-immersion and restraint stress-induced gastric mucosal injury in ratsBackground and ObjectiveCritically ill patients who are subjected to high stress is controversial about whether fasting clinically. In this section, the objective of the study is to investigative the influence of non-fasting and fasting treatments on water-immersion and restraint stress-induced gastric mucosal injury and the expression of MMP-9 and TIMP-2 in rats.MethodsStress ulcer model was established by water-immersion and restraint stress(WIRS). Not fasting group didn’t fasting, and fasting group did fasting 24 h before the stress. The rats mucosa was examined, and ulcer index(UI) was evaluated after 3 hours stress. Mucosa hemorrhage was determined at histology. In addition, the protein level of MMP-9 and TIMP-2 was measured by western blot.Results(1) The rats stress ulcer model had been established by WIRS at 3 hours.(2) The UI, inflammatory cells and protein level of MMP-9 in mucosa were more higher in fasting treatments group than in non-fasting treatments group(P < 0. 01). And the protein level of TIMP-2 in mucosa was slightly lower in fasting treatments group than in non-fasting treatments group, but there was no statistically significant difference(P > 0. 05).Conclusions These results reveal that non-fasting treatment can alleviate WIRS-induced gastric mucosal injury through significantly down-regulating the expression of MMP-9 in the rats.Section two: Alleviation role of Melatonin on water-immersion and restraint stress-induced gastric mucosal injury in ratsBackground and ObjectiveThe long-term application of gastric acid inhibitor may cause complications clinically, so it is necessary to explore other effect, less adverse reaction of drugs to prevent ulcers. Melatonin(MT) is a kind of neuroendocrine hormones in the human body. In recent years scientists found that MT have protective role for gastric ulcer of rats induced by indomethacin. However, does MT have protective role on WIRS-induced gastric mucosal injury in rats? This part is to investigative the protective effects of melatonin(MT) in gastric stress ulcer of rat and expression of MMP9, MMP2 and TIMP-2 in mucosa, stress ulcer model was established by water-immersion and restraint stress(WIRS).MethodsMelatonin at dose of 10、20、40、60mg/kg were administrated in different group of rat at 30 min before the onset of WIRS. The rat mucosa was examined and ulcer index were evaluated after 3 hours stress. Mucosa hemorrhage was determined at histology. In addition, the m RNA and protein level of MMP-9、MMP-2 and TIMP-2 was measured by PCR and western blot.ResultsThe results showed that pre-administration of melatonin can decrease the ulcer index(UI) and inflammatory cells in mucosa(P < 0. 01). In addition, the m RNA and protein level of MMP-9 and MMP-2 was increased, TIMP-2 was decreased in WIRS induced rat ulcer model(P < 0.01). Moreover, the m RNA and protein level of MMP-2 and MMP-9 was inhibited, while TIMP-2 was promoted by melatonin in stress induced ulcer(P < 0. 05 or P < 0. 01).ConclusionsThese results reveal the alleviation role of Melatonin on WIRS-induced gastric mucosal injury in rats, which may partly through regulating the expression of MMP2, MMP9 and TIMP-2.
Keywords/Search Tags:stress, gastric ulcer, MMPs, non-fasting, fasting, melatonin, extracellular matrix
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