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首页> 外文期刊>Journal of neuroinflammation >Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury
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Minocycline prevents retinal inflammation and vascular permeability following ischemia-reperfusion injury

机译：米诺环素可预防缺血再灌注损伤后的视网膜炎症和血管通透性

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Background Many retinal diseases are associated with vascular dysfunction accompanied by neuroinflammation. We examined the ability of minocycline (Mino), a tetracycline derivative with anti-inflammatory and neuroprotective properties, to prevent vascular permeability and inflammation following retinal ischemia-reperfusion (IR) injury, a model of retinal neurodegeneration with breakdown of the blood-retinal barrier (BRB). Methods Male Sprague–Dawley rats were subjected to 45 min of pressure-induced retinal ischemia, with the contralateral eye serving as control. Rats were treated with Mino prior to and following IR. At 48 h after reperfusion, retinal gene expression, cellular inflammation, Evan’s blue dye leakage, tight junction protein organization, caspase-3 activation, and DNA fragmentation were measured. Cellular inflammation was quantified by flow-cytometric evaluation of retinal tissue using the myeloid marker CD11b and leukocyte common antigen CD45 to differentiate and quantify CD11b+/CD45low microglia, CD11b+/CD45hi myeloid leukocytes and CD11bneg/CD45hi lymphocytes. Major histocompatibility complex class II (MHCII) immunoreactivity was used to determine the inflammatory state of these cells. Results Mino treatment significantly inhibited IR-induced retinal vascular permeability and disruption of tight junction organization. Retinal IR injury significantly altered mRNA expression for 21 of 25 inflammation- and gliosis-related genes examined. Of these, Mino treatment effectively attenuated IR-induced expression of lipocalin 2 (LCN2), serpin peptidase inhibitor clade A member 3 N (SERPINA3N), TNF receptor superfamily member 12A (TNFRSF12A), monocyte chemoattractant-1 (MCP-1, CCL2) and intercellular adhesion molecule-1 (ICAM-1). A marked increase in leukostasis of both myeloid leukocytes and lymphocytes was observed following IR. Mino treatment significantly reduced retinal leukocyte numbers following IR and was particularly effective in decreasing the appearance of MHCII+ inflammatory leukocytes. Surprisingly, Mino did not significantly inhibit retinal cell death in this model. Conclusions IR induces a retinal neuroinflammation within hours of reperfusion characterized by inflammatory gene expression, leukocyte adhesion and invasion, and vascular permeability. Despite Mino significantly inhibiting these responses, it failed to block neurodegeneration.
机译：背景技术许多视网膜疾病与血管功能障碍并发神经炎相关。我们检查了具有抗炎和神经保护特性的四环素衍生物美满霉素（Mino）预防视网膜缺血再灌注（IR）损伤后的血管通透性和炎症的能力。 （BRB）。方法对雄性Sprague–Dawley大鼠进行压力诱导的视网膜缺血45分钟，以对侧眼为对照。在IR之前和之后，用Mino治疗大鼠。再灌注后48小时，测量了视网膜基因表达，细胞炎症，Evan的蓝色染料泄漏，紧密连接蛋白组织，caspase-3激活和DNA断裂。通过使用髓样标记CD11b和白细胞共同抗原CD45对视网膜组织进行流式细胞术评估来量化细胞炎症，以区分和定量CD11b + / CD45low小胶质细胞，CD11b + / CD45hi髓样白细胞和CD11bneg / CD45hi淋巴细胞。主要的组织相容性复合体II类（MHCII）免疫反应性用于确定这些细胞的炎症状态。结果Mino治疗显着抑制IR诱导的视网膜血管通透性和紧密连接组织的破坏。视网膜IR损伤显着改变了所检查的25个炎症和神经胶质相关基因中21个的mRNA表达。其中，Mino处理可有效减弱IR诱导的脂蛋白2（LCN2），丝氨酸蛋白酶抑制剂肽酶抑制剂进化枝A成员3 N（SERPINA3N），TNF受体超家族成员12A（TNFRSF12A），单核细胞趋化因子-1（MCP-1，CCL2）的表达。和细胞间粘附分子-1（ICAM-1）。 IR后观察到髓样白细胞和淋巴细胞的白细胞停滞明显增加。 Mino治疗可显着减少IR后的视网膜白细胞数量，对减少MHCII +炎症性白细胞的出现特别有效。令人惊讶的是，在该模型中，Mino没有显着抑制视网膜细胞死亡。结论IR在再灌注后数小时内会诱发视网膜神经炎症，其特征在于炎症基因表达，白细胞粘附和侵袭以及血管通透性。尽管Mino明显抑制了这些反应，但它未能阻止神经变性。

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