Fang Rong, Zheng Xiaojun, Zhang Mei
Department of Neurosurgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
Department of Geriatrics, The First Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, China.
Acta Neurochir (Wien). 2016 Jun;158(6):1069-76. doi: 10.1007/s00701-016-2795-3. Epub 2016 Apr 12.
Previous studies have demonstrated the neuroprotective effects of ethyl pyruvate in central nervous system (CNS) diseases. However, whether ethyl pyruvate attenuates early brain injury after subarachnoid hemorrhage (SAH) remains unknown. This study was conducted to investigate the potential effects of ethyl pyruvate on early brain injury induced by SAH and explore the underlying mechanisms.
Eighty-eight male Sprague-Dawley rats were used. An SAH model was induced by endovascular perforation. Ethyl pyruvate (100 mg/kg) or a vehicle was administered intraperitoneally at 1 h after SAH induction. SAH grade, neurological scores, brain water content, Evans blue extravasation, Western blots, and immunofluorescence were used to study the mechanisms of ethyl pyruvate.
Ethyl pyruvate treatment inhibited microglia activation and reduced the expression of proinflammatory cytokines (IL-1β and TNF-α). Ethyl pyruvate treatment also prevented disruption of tight junction proteins (occluding and claudin-5) and reduced expression of MMP-9. In addition, ethyl pyruvate treatment markedly reduced TUNEL-positive cells and expression of cleaved caspase-3.
Our results indicated that ethyl pyruvate treatment attenuated early brain injury and improved neurological function after SAH by inhibiting microglia activation and apoptosis and stabilizing the BBB.
先前的研究已证明丙酮酸乙酯在中枢神经系统（CNS）疾病中的神经保护作用。然而，丙酮酸乙酯是否能减轻蛛网膜下腔出血（SAH）后的早期脑损伤仍不清楚。本研究旨在探讨丙酮酸乙酯对SAH所致早期脑损伤的潜在影响，并探索其潜在机制。
使用88只雄性Sprague-Dawley大鼠。通过血管内穿刺诱导SAH模型。在SAH诱导后1小时腹腔注射丙酮酸乙酯（100mg/kg）或溶剂。采用SAH分级、神经功能评分、脑含水量、伊文思蓝外渗、蛋白质免疫印迹法和免疫荧光法研究丙酮酸乙酯的作用机制。
丙酮酸乙酯治疗可抑制小胶质细胞活化，并降低促炎细胞因子（IL-1β和TNF-α）的表达。丙酮酸乙酯治疗还可防止紧密连接蛋白（闭合蛋白和claudin-5）的破坏，并降低MMP-9的表达。此外，丙酮酸乙酯治疗可显著减少TUNEL阳性细胞和裂解的caspase-3的表达。
我们的结果表明，丙酮酸乙酯治疗可通过抑制小胶质细胞活化和凋亡以及稳定血脑屏障来减轻SAH后的早期脑损伤并改善神经功能。
