Swarnakar Snehasikta, Mishra Amartya, Ganguly Krishnendu, Sharma Anamika Vivek
Department of Physiology, Indian Institute of Chemical Biology, Kolkata, India.
J Pineal Res. 2007 Aug;43(1):56-64. doi: 10.1111/j.1600-079X.2007.00443.x.
Matrix metalloproteinases (MMPs) play an important role in degradation of gastric extracellular matrix proteins. However, no reports are available on the relationship between the activity of MMPs and gastric ulceration induced by alcohol. Our objective was to investigate the effect of melatonin (N-acetyl-5-methoxytryptamine) on the regulation of MMP-9 and MMP-2 activities during prevention of ethanol-induced gastric ulcer. Biochemical and zymographic methods were used to analyze MMP-9 and -2 activities in gastric tissues of Balb/c mice following induction of gastric ulcer by ethanol. Our studies reveal that melatonin arrested cell injury, protein carbonyl formation, and lipid peroxidation in mice during gastroprotection. Melatonin dose-dependently reduced proMMP-9 activity that was induced ( approximately 25-fold) during ethanol-induced gastric ulceration. Severity of gastric ulcers were correlated proportionately with increased dose of ethanol and elevated activity of proMMP-9 and -2. The reduced activities of MMP-9 and -2 were associated with reduced expression of TNF-alpha and increased expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2). We conclude that melatonin's ability to prevent ethanol-induced gastric ulceration in mice is related to a reduction in proMMP-9 activity and expression.
基质金属蛋白酶（MMPs）在胃细胞外基质蛋白的降解中起重要作用。然而，关于MMPs活性与酒精诱导的胃溃疡之间的关系尚无报道。我们的目的是研究褪黑素（N-乙酰-5-甲氧基色胺）在预防乙醇诱导的胃溃疡过程中对MMP-9和MMP-2活性调节的影响。采用生化和酶谱法分析乙醇诱导Balb/c小鼠胃溃疡后胃组织中MMP-9和-2的活性。我们的研究表明，褪黑素在胃保护过程中可阻止小鼠的细胞损伤、蛋白质羰基形成和脂质过氧化。褪黑素剂量依赖性地降低了乙醇诱导胃溃疡期间诱导的（约25倍）前MMP-9活性。胃溃疡的严重程度与乙醇剂量增加以及前MMP-9和-2活性升高成比例相关。MMP-9和-2活性降低与TNF-α表达降低以及金属蛋白酶组织抑制剂（TIMP-1和TIMP-2）表达增加有关。我们得出结论，褪黑素预防小鼠乙醇诱导胃溃疡的能力与前MMP-9活性和表达的降低有关。
