Qiu Jian, Wang Xin, Wu Fei, Wan Lei, Cheng Baohua, Wu Yili, Bai Bo
School of Medicine, Shandong University, Jinan, China.
Institute of Neurobiology, Jining Medical University, Jining, China.
Front Neurol. 2017 Oct 16;8:556. doi: 10.3389/fneur.2017.00556. eCollection 2017.
Cerebral ischemia/reperfusion (I/R) injury-induced cellular apoptosis contributes to neuronal death in ischemic stroke, while endoplasmic reticulum stress (ERS) and subsequently triggered unfolded protein response (UPR) are the major mechanisms of cerebral I/R injury-induced apoptosis. A number of studies indicated that apelin-13 protects neurons from I/R injury-induced apoptosis. Apelin-36, the longest isoform of apelin, has stronger affinity to apelin receptor than apelin-13 does. However, the role of apelin-36 in ischemic stroke is less studied. In addition, preventive administration of apelin was applied in most studies, which could not precisely reflect its therapeutic potential in ischemic stroke. Here, we first reported that low dose of apelin-36, other than apelin-13, administrated after ischemic stroke significantly reduced infarct volume in rats. Moreover, apelin-36 attenuated cerebral I/R injury-induced apoptosis and caspase-3 activation. Furthermore, apelin-36 suppressed I/R injury-induced CHOP and GRP78 elevation, indicating that apelin-36 inhibited ERS/UPR activation. Our study first demonstrated that post-stroke administration of low-dose apelin-36 could attenuate cerebral I/R injury-induced infarct and apoptosis, which is associated with the inhibition of cerebral I/R injury-induced ERS/UPR activation. Our data support the therapeutic potential of apelin-36 in ischemic stroke although further investigation is needed.
脑缺血/再灌注（I/R）损伤诱导的细胞凋亡促使缺血性卒中的神经元死亡，而内质网应激（ERS）及随后触发的未折叠蛋白反应（UPR）是脑I/R损伤诱导凋亡的主要机制。多项研究表明，apelin-13可保护神经元免受I/R损伤诱导的凋亡。Apelin-36是apelin最长的异构体，其对apelin受体的亲和力比apelin-13更强。然而，apelin-36在缺血性卒中中的作用研究较少。此外，大多数研究采用apelin预防性给药，这无法准确反映其在缺血性卒中中的治疗潜力。在此，我们首次报道，缺血性卒中后给予低剂量的apelin-36而非apelin-13可显著降低大鼠梗死体积。此外，apelin-36减轻了脑I/R损伤诱导的凋亡和caspase-3激活。此外，apelin-36抑制了I/R损伤诱导的CHOP和GRP78升高，表明apelin-36抑制了ERS/UPR激活。我们的研究首次证明，卒中后给予低剂量apelin-36可减轻脑I/R损伤诱导的梗死和凋亡，这与抑制脑I/R损伤诱导的ERS/UPR激活有关。尽管需要进一步研究，但我们的数据支持apelin-36在缺血性卒中中的治疗潜力。
