Abstract: Objective To investigative the protective effects of melatonin (MT) in gastric stress ulcer of rat and expression of MMP9, MMP2 and TIMP-2 in mucosa. Methods Stress ulcer model was established by water-immersion and restraint stress (WIRS). Melatonin 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 mRNA and protein level of MMP9、MMP2 and TIMP-2 was measured by PCR and western blot. Results The rat stress ulcer model can be established by WIRS at 3 hours. Pre-administration of melatonin can decrease the ulcer index (UI) and inflammatory cells in mucosa（P ＜ 0. 01). In addition, the mRNA and protein level of MMP9 and MMP2 was increased, TIMP-2 was decreased in WIRS induced rat ulcer model (P ＜ 0.01). Moreover, the mRNA and protein level of MMP2 and MMP9 was inhibited, while TIMP-2 was promoted by melatonin in stress induced ulcer（P ＜ 0. 05 or P ＜ 0. 01). Conclusions These 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 TIMP2.

Key words: stress, gastric ulcer, melatonin, MMPs, extracellular matrix