Department of Pharmacology, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University School of Medicine, Yangsan 626-870, Korea.
Korean J Physiol Pharmacol. 2011 Apr;15(2):115-22. doi: 10.4196/kjpp.2011.15.2.115. Epub 2011 Apr 30.
The aim of this study was to investigate whether matrix metalloproteinase (MMP) inhibitors attenuate neuroinflammation in an ischemic brain following photothrombotic cortical ischemia in mice. Male C57BL/6 mice were anesthetized, and Rose Bengal was systemically administered. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold white light. MMP inhibitors, such as doxycycline, minocycline, and batimastat, significantly reduced the cerebral infarct size, and the expressions of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and indoleamine 2,3-dioxygenase (IDO). However, they had no effect on the expressions of heme oxygenase-1 and neuroglobin in the ischemic cortex. These results suggest that MMP inhibitors attenuate ischemic brain injury by decreasing the expression levels of MCP-1, TNF-α, and IDO, thereby providing a therapeutic benefit against cerebral ischemia.
本研究旨在探讨基质金属蛋白酶（MMP）抑制剂是否能减轻光血栓性大脑皮层缺血后小鼠缺血性大脑中的神经炎症。雄性 C57BL/6 小鼠麻醉后，全身给予 Rose Bengal。通过用冷白光照射颅骨，在额中回和体感皮层诱导永久性局灶性缺血。MMP 抑制剂，如强力霉素、米诺环素和 batimastat，显著减小脑梗死面积，并降低单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）和吲哚胺 2,3-双加氧酶（IDO）的表达。然而，它们对缺血皮质中血红素加氧酶-1 和神经球蛋白的表达没有影响。这些结果表明，MMP 抑制剂通过降低 MCP-1、TNF-α 和 IDO 的表达水平来减轻缺血性脑损伤，从而为脑缺血提供治疗益处。
