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首页> 外文期刊>Brain research >Probenecid protects against oxygen-glucose deprivation injury in primary astrocytes by regulating inflammasome activity
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Probenecid protects against oxygen-glucose deprivation injury in primary astrocytes by regulating inflammasome activity

机译：丙磺舒通过调节炎症小体活性来保护原代星形胶质细胞免受氧葡萄糖剥夺的伤害

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Inflammation is extremely important in the development of cerebral ischemia/reperfusion injury. Pannexin 1 (Panx1) channel has been reported to activate inflammasome in astrocytes and be involved in ischemic injury, but this damage effect is reversed by a Panx1 inhibitor probenecid. However, the mechanism of probenecid protects against cerebral ischemia/reperfusion injury remains unclear. In present study, we hypothesized that probenecid protected astrocytes from ischemia/reperfusion injury in vitro by modulating the inflammasome. Primary cultured neocortical astrocytes were exposed to oxygen-glucose deprivation/reoxygenation (OGD/RX) and probenecid was added in this model. Viability and nuclear morphology of astrocytes, production of reactive oxygen species (ROS), protein expressions of NLRP3 (NOD-like receptor protein 3), caspase-1, and AQP4 (Aquaporins 4), as well as release of cellular HMGB1 and IL-1 beta were observed to evaluate the effect and mechanisms of probenecid on OGD/reoxygenated astrocytes. Probenecid did not affect cell viability at concentrations of 1, 5, 10, and 100 mu M but induced significant astrocytes death at 500 mu M. Probenecid inhibited cell death and ROS generation in astrocytes subjected to 6 h of OGD and 24 h of reoxygenation. The expression levels of NLRP3, caspase-1, and AQP4 increased after 6 h of OGD, but probenecid treatment attenuated this increase. Moreover, the extracellular release of IL-1 beta and HMGB1 from OGD/reoxygenated astrocytes increased significantly. However, treatment by probenecid resulted in substantial reduction of these proteins levels in extra cellular space. In conclusion, The Panx1 inhibitor, probenecid, which was administered before OGD, provided protective effects on the OGD/reoxygenation model of cultured astrocytes by modulating inflammasome activity and downregulating AQP4 expression. (c) 2016 Elsevier B.V. All rights reserved.
机译：炎症在脑缺血/再灌注损伤的发生中极为重要。据报道，Pannexin 1（Panx1）通道可激活星形胶质细胞中的炎性体并参与缺血性损伤，但Panx1抑制剂丙磺舒可逆转这种损伤作用。然而，丙磺舒预防脑缺血/再灌注损伤的机制仍不清楚。在本研究中，我们假设丙磺舒可通过调节炎症小体在体外保护星形胶质细胞免受缺血/再灌注损伤。将原代培养的新皮质星形胶质细胞暴露于氧-葡萄糖剥夺/复氧（OGD / RX），并在该模型中添加丙磺舒。星形胶质细胞的活力和核形态，活性氧（ROS）的产生，NLRP3（NOD样受体蛋白3），caspase-1和AQP4（水通道蛋白4）的蛋白表达，以及细胞HMGB1和IL-的释放观察到1个beta来评估丙磺舒对OGD /复氧星形胶质细胞的作用和机制。丙磺舒在浓度为1、5、10和100μM时不会影响细胞活力，但在500μM时会引起星形胶质细胞的明显死亡。丙磺舒抑制了经过6 h的OGD和24 h复氧的星形胶质细胞的细胞死亡和ROS的产生。 OGD 6小时后，NLRP3，caspase-1和AQP4的表达水平增加，但丙磺舒治疗降低了这种增加。此外，从OGD /复氧星形胶质细胞中IL-1β和HMGB1的细胞外释放显着增加。然而，丙磺舒的治疗导致细胞外空间中这些蛋白质水平的显着降低。总之，在OGD之前使用的Panx1抑制剂丙磺舒通过调节炎症小体活性和下调AQP4表达，对培养的星形胶质细胞的OGD /复氧模型具有保护作用。 （c）2016 Elsevier B.V.保留所有权利。

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