Allen Rachael S, Sayeed Iqbal, Oumarbaeva Yuliya, Morrison Katherine C, Choi Paul H, Pardue Machelle T, Stein Donald G
Department of Emergency Medicine, Emory University, Atlanta, GA, USA.
Department of Ophthalmology, Emory University, Atlanta, GA, USA.
Restor Neurol Neurosci. 2016 Nov 22;34(6):947-963. doi: 10.3233/RNN-160672.
BACKGROUND/OBJECTIVE: To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain.
MCAO rats treated systemically with progesterone or vehicle were compared with shams. Protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane X receptor were assessed in retinas and brains at 24 and 48 h using western blots.
Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κB and CD11b at 24 h in both brain and retina, nuclear NF-κB at 24 h in brain and 48 h in retina, and TNF-α at 24 h in brain.Progesterone treatment in MCAO animals significantly attenuated levels of the following markers in brain: pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b, with significantly increased levels of cytosolic NF-κB. Retinas from progesterone-treated animals showed significantly reduced levels of nuclear NF-κB and IL-6 and increased levels of cytosolic NF-κB, with a trend for reduction in other markers. Post-MCAO, progesterone receptors A and B were upregulated in brain and downregulated in retina.
Inflammatory markers increased in both brain and retina after MCAO, with greater increases observed in brain. Progesterone treatment reduced inflammation, with more dramatic reductions observed in brain than retina. This differential effect may be due to differences in the response of progesterone receptors in brain and retina after injury.
背景/目的：确定大脑中动脉闭塞（MCAO）后视网膜炎症是否像大脑炎症一样增加，以及神经甾体孕酮在MCAO后对视网膜和大脑均显示出保护作用，是否也能减轻视网膜炎症。
将全身用孕酮或赋形剂处理的MCAO大鼠与假手术组大鼠进行比较。在24小时和48小时时，使用蛋白质印迹法评估视网膜和大脑中细胞质NF-κB、细胞核NF-κB、磷酸化NF-κB、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、CD11b、孕酮受体A和B以及孕烷X受体的蛋白质水平。
MCAO后，观察到以下炎症标志物显著增加：大脑和视网膜中24小时时的磷酸化NF-κB和CD11b，大脑中24小时时和视网膜中48小时时的细胞核NF-κB，以及大脑中24小时时的TNF-α。对MCAO动物进行孕酮治疗可显著降低大脑中以下标志物的水平：磷酸化NF-κB、细胞核NF-κB、IL-6、TNF-α和CD11b，同时细胞质NF-κB水平显著升高。孕酮处理动物的视网膜显示细胞核NF-κB和IL-6水平显著降低，细胞质NF-κB水平升高，其他标志物有降低趋势。MCAO后，孕酮受体A和B在大脑中上调，在视网膜中下调。
MCAO后大脑和视网膜中的炎症标志物均增加，大脑中的增加更为明显。孕酮治疗可减轻炎症，大脑中的减轻程度比视网膜更显著。这种差异效应可能是由于损伤后大脑和视网膜中孕酮受体反应的差异所致。
