Ethyl Pyruvate Attenuates Early Brain Injury Following Subarachnoid Hemorrhage in the Endovascular Perforation Rabbit Model Possibly Via Anti-inflammation and Inhibition of JNK Signaling Pathway
Ethyl Pyruvate Attenuates Early Brain Injury Following Subarachnoid Hemorrhage in the Endovascular Perforation Rabbit Model Possibly Via Anti-inflammation and Inhibition of JNK Signaling Pathway
复制标题
丙酮酸乙酯可能通过抗炎和抑制 JNK 信号通路减轻血管内穿孔兔模型中蛛网膜下腔出血后的早期脑损伤
DOI：
10.1007/s11064-016-2138-z
复制
发表时间：
2017-04-01
影响因子：
4.4
通讯作者：
Zhang, Xiao-Hua
中科院分区：
文献类型：
--
作者：
Lv, Tao;Miao, Yi-Feng;Zhang, Xiao-Hua
蛛网膜下腔出血（SAH）后的早期脑损伤（EBI）是SAH患者预后不良的主要原因，早期炎症在急性病理生理事件中起重要作用。已有研究表明丙酮酸乙酯（EP）在多种危重病中具有抗炎和神经保护作用，然而，EP在SAH后EBI中的作用仍有待阐明。我们的研究旨在评估EP对血管内穿刺兔模型中SAH后EBI的影响。所有兔子随机分为三组：假手术组、SAH + 溶媒（等体积）组和SAH + EP（30mg/kg/天）组。在SAH后24小时和72小时进行磁共振成像（MRI）以评估EBI的可靠性。记录神经功能评分以评估神经功能缺损，采用酶联免疫吸附测定（ELISA）试剂盒测量肿瘤坏死因子 -α（TNF -α）水平，并在SAH后24小时和72小时采用蛋白质印迹法检测TNF -α、tJNK、pJNK、bax和bcl - 2的表达。采用脱氧核糖核苷酸末端转移酶介导的dUTP缺口末端标记法（TUNEL）和荧光玉红B（FJB）染色分别检测神经元凋亡和神经变性，同时采用苏木精 - 伊红（H&E）染色评估血管痉挛程度。我们的结果表明，EP减轻了脑组织损伤（以MRI扫描中的弥散加权成像和T2序列为特征），并在SAH后72小时显著改善了神经功能评分。EP在SAH后24小时和72小时均有效降低了大脑皮质和海马中TNF -α的水平，并下调了pJNK/tJNK和bax/bcl - 2。此外，EP显著减少了TUNEL和FJB阳性细胞。总之，本研究支持EP可能通过降低TNF -α表达和抑制JNK信号通路提供神经保护作用。因此，EP可能是一种减轻SAH后EBI的有效治疗药物。
Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is the main cause to poor outcomes of SAH patients, and early inflammation plays an important role in the acute pathophysiological events. It has been demonstrated that ethyl pyruvate (EP) has anti-inflammatory and neuroprotective effects in various critical diseases, however, the role of EP on EBI following SAH remains to be elucidated. Our study aimed to evaluate the effects of EP on EBI following SAH in the endovascular perforation rabbit model. All rabbits were randomly divided into three groups: sham, SAH + Vehicle (equal volume) and SAH + EP (30 mg/kg/day). MRI was performed to estimate the reliability of the EBI at 24 and 72 h after SAH. Neurological scores were recorded to evaluate the neurological deficit, ELISA kit was used to measure the level of tumor necrosis factor-α (TNF-α), and western blot was used to detect the expression of TNF-α, tJNK, pJNK, bax and bcl-2 at 24 and 72 h after SAH. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB) staining were used to detect neuronal apoptosis and neurodegeneration respectively, meanwhile hematoxylin and eosin (H&E) staining was used to assess the degree of vasospasm. Our results demonstrated that EP alleviated brain tissue injury (characterized by diffusion weighted imaging and T2 sequence in MRI scan), and significantly improved neurological scores at 72 h after SAH. EP decreased the level of TNF-α and downregulated pJNK/tJNK and bax/bcl-2 in cerebral cortex and hippocampus effectively both at 24 and 72 h after SAH. Furthermore, EP reduced TUNEL and FJB positive cells significantly. In conclusion, the present study supported that EP afforded neuroprotective effects possibly via reducing TNF-α expression and inhibition of the JNK signaling pathway. Therefore, EP may be a potent therapeutic agent to attenuate EBI following SAH.