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首页> 外文期刊>Cytokine >Effects of recombinant human erythropoietin (rhEPO) on JAK2/STAT3 pathway and endothelial apoptosis in the rabbit basilar artery after subarachnoid hemorrhage.
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Effects of recombinant human erythropoietin (rhEPO) on JAK2/STAT3 pathway and endothelial apoptosis in the rabbit basilar artery after subarachnoid hemorrhage.

机译:重组人促红细胞生成素(rhEPO)对蛛网膜下腔出血后兔基底动脉JAK2 / STAT3通路和内皮细胞凋亡的影响。

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Previous studies have shown that recombinant human erythropoietin (rhEPO) can attenuate the degree of cerebral vasospasm following experimental subarachnoid hemorrhage (SAH). However, the mechanisms for this beneficial effect are still poorly understood. SAH-induced endothelial apoptosis may trigger, aggravate, and maintain cerebral vasospasm. We, therefore, tried to analyze whether rhEPO administration influenced the endothelial cell apoptosis in the basilar artery after SAH. Another aim of the current study was to investigate the modulation of rhEPO on the activity of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), which played an important role in the signaling of apoptosis. A total of 48 rabbits were randomly divided into four groups; control group, SAH group, SAH+vehicle group, and SAH+rhEPO group. All SAH animals were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2. The rhEPO was administered i.p. starting 5 min after the induction of SAH on day 0 and repeated every 8 h for 120 h. The basilar arteries were extracted on day 5 after SAH. As a result, we found that administration of rhEPO could activate JAK2 and STAT3 in the basilar artery and decrease the apoptosis index of endothelial cells following SAH. Moreover, the anti-apoptotic genes such as bcl-2 and bcl-xL were up-regulated after the injections of rhEPO. In conclusion, the therapeutic effect of rhEPO on the subsequent vasospasm after SAH may relate to its inhibition on the endothelial apoptosis in the cerebral arteries, which may be mediated in part by JAK2/STAT3 signaling pathway.
机译:先前的研究表明,重组人促红细胞生成素(rhEPO)可以减轻实验性蛛网膜下腔出血(SAH)后脑血管痉挛的程度。但是,对于这种有益作用的机制仍知之甚少。 SAH诱导的内皮细胞凋亡可能触发,加重和维持脑血管痉挛。因此,我们试图分析rhEPO给药是否会影响SAH后基底动脉中的内皮细胞凋亡。本研究的另一个目的是研究rhEPO对Janus激酶2(JAK2)以及信号转导和转录激活因子3(STAT3)的活性的调节,这在细胞凋亡的信号传导中起重要作用。将48只兔随机分为四组。对照组,SAH组,SAH +车辆组和SAH + rhEPO组。在第0天和第2天,两次对所有SAH动物进行自体血向大水罐的注射两次。从第0天SAH诱导后5分钟开始,每8小时重复120小时。在SAH后第5天提取基底动脉。结果,我们发现,rhEPO的给药可以激活SAH后基底动脉中的JAK2和STAT3,并降低内皮细胞的凋亡指数。此外,注射rhEPO后,抗凋亡基因如bcl-2和bcl-xL被上调。总之,rhEPO对SAH后继发的血管痉挛的治疗作用可能与其对脑动脉内皮细胞凋亡的抑制有关,其可能部分由JAK2 / STAT3信号通路介导。

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