Shi Lei, Wang Zaizong, Liu Xianjin, Li Mao, Zhang Shangfei, Song Xiaobin
a Department of Neurosurgery , Zhumadian Central Hospital , Zhumadian , China.
b Department of Neurosurgery , The First Affiliated Hospital of Kunming Medical College , Kunming , China.
Neurol Res. 2018 Mar;40(3):189-196. doi: 10.1080/01616412.2018.1424699. Epub 2018 Jan 16.
Background and Purpose Bax inhibitor-1 (BI-1) has been identified as a suppressor of Bax-mediated cell apoptosis by regulation of endoplasmic reticulum stress-induced cell death. However, the role of BI-1 in Early Brain Injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. In the present study, we aim to explore the neuroprotective functions of BI-1 in EBI after SAH by using models of SAH that induced endovascular perforation in rats. Method The neurological score, brain water content and blood-brain barrier (BBB) permeability were evaluated simultaneously as prognostic indicators. Western blot, RT-PCR and TUNEL staining were performed to study the role and mechanisms of BI-1 in EBI after SAH. Results We found that BI-1 knockdown increased histological injury and the percentages of TUNEL-positive neuron in hippocampal, promoted the expressions of endoplasmic reticulum (ER) stress proteins inositol-requiring enzyme 1α (IRE1α) and TNF receptor-associated factor 2 (TRAF2), and increased the activation levels of apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) in the hippocampus of SAH rats compared with rats in SAH + vehicle group. Conclusion Our results indicate that BI-1 may participate in the regulation of EBI after SAH by regulating IRE1-JNK pathway. Thus, the results suggest that BI-1 may be a potential therapeutic target for SAH treatment.
背景与目的 Bax抑制剂-1（BI-1）已被确定为通过调节内质网应激诱导的细胞死亡来抑制Bax介导的细胞凋亡。然而，BI-1在蛛网膜下腔出血（SAH）后早期脑损伤（EBI）中的作用仍不清楚。在本研究中，我们旨在通过使用诱导大鼠血管内穿孔的SAH模型来探讨BI-1在SAH后EBI中的神经保护功能。方法 同时评估神经功能评分、脑含水量和血脑屏障（BBB）通透性作为预后指标。进行蛋白质免疫印迹法、逆转录-聚合酶链反应（RT-PCR）和TUNEL染色以研究BI-1在SAH后EBI中的作用和机制。结果 我们发现，与SAH+载体组大鼠相比，在SAH大鼠海马中，BI-1基因敲低增加了组织学损伤和TUNEL阳性神经元的百分比，促进了内质网（ER）应激蛋白肌醇需求酶1α（IRE1α）和肿瘤坏死因子受体相关因子2（TRAF2）的表达，并增加了凋亡信号调节激酶1（ASK1）和c-Jun氨基末端激酶（JNK）的激活水平。结论 我们的结果表明，BI-1可能通过调节IRE1-JNK途径参与SAH后EBI的调节。因此，结果表明BI-1可能是SAH治疗的潜在治疗靶点。
