Brain EGR1 (early growth response protein 1) overexpression aggravates focal ischemic brain injury, but its role in intracerebral hemorrhage (ICH) induced cerebral injury remains obscure. In this study, a rat ICH model was established by injecting type VII collagenase into the brain, and EGR1 knockdown reversed the increase of hematoma area, neurological function score, brain water content, blood–brain barrier (BBB) permeability, inflammation, p300 and retinoid a X receptor-α (RXRα) protein levels, as well as RXRα acetylation level induced by ICH. EGR1 expression was up-regulated in primary brain microvascular endothelial cells (BMECs), neurons, and astrocytes after ICH induction, and the up-regulation was most significant in BMECs. We also found that EGR1 promoted RXRα acetylation level by regulating p300 in BMECs. Silencing EGR1 rescued the upregulation of cell inflammation and the reduction of cell viability and TEER (transendothelial electric resistance) caused by OGD (oxygen glucose deprivation) plus hemin via p300-mediated RXRα acetylation. Furthermore, the STAT3/NF-κB pathway was activated after treatment with OGD plus hemin, which was suppressed by silencing EGR1. Treatment with Stattic (an inhibitor of STAT3) restrained the effect of OGD plus hemin on NF-κB pathway activity, inflammation, cell viability and TEER. In conclusion, EGR1 increased RXRα acetylation level by regulating p300, thereby aggravating brain damage in ICH rat model and dysfunction in BMECs, Through the STAT3/NF-κB pathway.

脑 EGR1（早期生长反应蛋白 1）过度表达会加重局灶性缺血性脑损伤，但其在脑出血 (ICH) 诱导的脑损伤中的作用仍不清楚。本研究通过向脑内注射 VII 型胶原酶建立大鼠 ICH 模型，敲低 EGR1 逆转血肿面积、神经功能评分、脑含水量、血脑屏障 (BBB) 通透性、炎症、p300 和维甲酸 a X 受体-α (RXRα) 蛋白水平，以及 ICH 诱导的 RXRα 乙酰化水平。在 ICH 诱导后，EGR1 在原代脑微血管内皮细胞 (BMECs)、神经元和星形胶质细胞中的表达上调，其中上调在 BMECs 中最为显着。我们还发现 EGR1 通过调节 BMECs 中的 p300 来促进 RXRα 乙酰化水平。沉默 EGR1 通过 p300 介导的 RXRα 乙酰化挽救了由 OGD（氧葡萄糖剥夺）加血红素引起的细胞炎症的上调以及细胞活力和 TEER（跨内皮电阻）的降低。此外，在用 OGD 加血红素处理后，STAT3/NF-κB 通路被激活，这被 EGR1 沉默所抑制。Stattic（一种 STAT3 抑制剂）治疗抑制了 OGD 加血红素对 NF-κB 通路活性、炎症、细胞活力和 TEER 的影响。总之，EGR1 通过调节 p300 增加 RXRα 乙酰化水平，从而通过 STAT3/NF-κB 通路加重 ICH 大鼠模型的脑损伤和 BMECs 的功能障碍。