褪黑素减轻浸水-束缚应激大鼠胃黏膜损伤

Melatorin alleviates gastric mucosal injury induced by water-immersion and restraint seress in rats

目的探讨褪黑素(MT)对大鼠应激性胃溃疡的保护作用及对胃黏膜MMP-9、MMP-2和TIMP-2表达的影响。方法用浸水-束缚应激(WIRS)建立大鼠应激性溃疡模型。应激前30 min,分别腹腔注射褪黑素10、20、40和60 mg/kg。应激3 h后,观察大鼠胃黏膜病变,对溃疡指数(UI)进行评分;组织学观察胃出血;用real-time PCR及Western blot检测胃黏膜MMP-9、MMP-2和TIMP-2的mRNA及蛋白表达。结果 WIRS应激3 h能成功诱导大鼠应激性胃溃疡。预先注射MT可明显降低应激性胃溃疡大鼠的UI(P<0.01),明显降低黏膜层炎性细胞浸润数(P<0.01)。WIRS诱导大鼠胃黏膜MMP-9和MMP-2 mRNA和蛋白表达上调(P<0.01),TIMP-2则下降;MT预处理后,MMP-2/MMP-9明显下降(P<0.05或P<0.01);而TIMP-2的mRNA及蛋白表达增加(P<0.05或P<0.01)。结论MT可能通过下调MMP-9和MMP-2表达,及增加TIMP-2表达,减轻WIRS诱导的大鼠应激性胃溃疡。

Objective To investigative the protective effects of melatonin（ MT） in gastric stress ulcer of rat and expression of MMP-9,MMP-2 and TIMP-2 in mucosa. Methods Stress ulcer model was established by water-immersion and restraint stress（ WIRS）. Melatonin at dose of 10,20,40,60 mg / kg were administrated in different group of rat at 30 min before the onset of WIRS. The rat mucosa was examined and ulcer index was evaluated after 3hours stress. Mucosa hemorrhage was determined by histology. In addition,the mRNA and protein levels of MMP-9,MMP-2 and TIMP-2 were 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 MMP-9 and MMP-2 was increased,TIMP-2 was decreased in WIRS induced rat ulcer model（ P 0. 01）. Moreover,the mRNA 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）. Conclusions The alleviation role of Melatonin on WIRS-induced gastric mucosal injury in rats may partly exert through regulating the expression of MMP-2,MMP-9 and TIMP-2.