Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.

中文翻译：

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乌司他丁通过减少 endothelin-1 减轻创伤性脑损伤

背景脑水肿是与损伤和神经外科手术相关的死亡和残疾的主要原因之一。本研究的目的是评估乌司他丁 (UTI)，一种蛋白酶抑制剂，对创伤性脑损伤 (TBI) 大鼠模型中星形胶质细胞的影响。方法建立TBI大鼠模型。将动物随机分为两组——一组用生理盐水治疗，第二组用尿路感染（50,000 U/kg）治疗。与假手术组（无 TBI）一起评估了两组的脑含水量和血脑屏障的通透性。通过免疫组织化学和蛋白质印迹测量胶质纤维酸性蛋白、内皮素-1 (ET-1)、血管内皮生长因子 (VEGF) 和基质金属蛋白酶 9 (MMP-9) 的表达。通过蛋白质印迹测量UTI对ERK和PI3K/AKT信号通路的影响。结果 UTI 显着降低了伊文思蓝染料的脑含水量和外渗。这种衰减与星形胶质细胞和 ET-1 的活化减少有关。UTI 治疗降低了 ERK 和 Akt 活化并抑制了促炎 VEGF 和 MMP-9 的表达。结论 UTI可通过抑制星形胶质细胞活化和ET-1产生来缓解TBI所致脑水肿。