研究领域：神经科学 药理学 分子生物学

关键字：OM-LV20 神经保护作用 脑缺血/再灌注损伤 大鼠梗死区域 行为异常 皮层和海马神经元 MAPK信号通路 BDNF/AKT信号通路 环腺苷酸 垂体腺苷酸环化酶激活多肽受体 色氨酸羟化酶1

缺血/再灌注（I/R）是导致缺血性脑卒中的常见损伤。目前，I/R的治疗手段仍十分有限，亟需发现和开发新型脑损伤保护药物。本研究探讨了前期从两栖动物中鉴定获得的短肽OM-LV20对I/R大鼠的神经保护作用。结果表明，腹腔注射OM-LV20（20 ng/kg）可显著减少脑梗死面积、改善行为学异常，并保护皮层及海马神经元免于I/R所致的死亡。其潜在分子机制涉及调控MAPK和BDNF/AKT信号通路，以及环磷酸腺苷、垂体腺苷酸环化酶激活多肽受体和色氨酸羟化酶1的表达水平。据我们所知，本研究首次报道了源自两栖动物皮肤分泌物的肽类物质在I/R大鼠模型中的神经保护作用，并凸显OM-LV20作为新型抗脑卒中治疗药物候选物的潜力。Ischemia/reperfusion (I/R) is a common injury leading to ischemic stroke. At present, I/R treatment remains limited, highlighting the urgent need for the discovery and development of new protective drugs for brain injury. Here, we investigated the neuroprotective effects of short peptide OM-LV20 previously identified from amphibian against I/R rats. Results showed that intraperitoneal administration of OM-LV20 (20 ng/kg) significantly reduced infarct area formation, improved behavioral abnormalities, and protected cortical and hippocampal neurons against death caused by I/R. Moreover, the underlying molecular mechanism was involved with the regulation of the MAPK and BDNF/AKT signaling pathways , as well as the levels of cyclic adenosine monophosphate , pituitary adenylate cyclase-activating polypeptide receptor, and tryptophan hydroxylase 1. To the best of our knowledge, this research was the first report to describe the neuroprotective effects of an amphibian skin secretion-derived peptide in I/R rats and highlighted OM-LV20 as a promising drug candidate for the development of novel anti-stroke therapies.