Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, Yunnan, China.
Endocrinology Department of affiliated Hospital of Yunnan University, Kunming 650021, Yunnan, China.
Exp Neurol. 2022 Nov;357:114180. doi: 10.1016/j.expneurol.2022.114180. Epub 2022 Jul 25.
Cerebral ischemia-reperfusion (I/R) is the main cause of neurological injury after stroke. However, existing treatments for I/R injury are relatively poor, and relevant drugs need to be further explored. Amphibians have received increasing attention as a resource bank of bioactive peptides. However, reports on neuroprotective peptides from amphibians remain extremely rare. Here, we identified a new neuroprotective peptide (OL-FS13, amino acid sequence: FSLLLTWWRRRVC) from the odorous frog species Odorrana livida using a constructed cDNA library. OL-FS13 significantly improving infarct volume, behavioral and histological abnormalities in rats, and also showed neuroprotective activities in PC12 cell (by oxygen glucose deprivation/reoxygenation, OGD/R). Mechanistically, OL-FS13 increased the level of antioxidative enzymes to resist oxidative stress and alleviated endoplasmic reticulum (ER) stress induced by I/R and OGD/R. The use of ML385 (Nrf2 inhibitor) indicated that OL-FS13 relieved nerve damage caused by oxidative and ER stress by increasing the nuclear displacement of Nrf2. Collectively, this research provides a novel drug candidate for the clinical cerebral I/R curation.
脑缺血再灌注（I/R）是中风后神经损伤的主要原因。然而，现有的 I/R 损伤治疗方法相对较差，需要进一步探索相关药物。两栖动物作为生物活性肽的资源库受到越来越多的关注。然而，关于两栖动物的神经保护肽的报道仍然非常罕见。在这里，我们使用构建的 cDNA 文库从臭蛙物种 Odorrana livida 中鉴定出一种新的神经保护肽（OL-FS13，氨基酸序列：FSLLLTWWRRRVC）。OL-FS13 显著改善了大鼠的梗死体积、行为和组织学异常，并且在 PC12 细胞（通过氧葡萄糖剥夺/再氧合，OGD/R）中也表现出神经保护活性。在机制上，OL-FS13 通过增加抗氧化酶的水平来抵抗氧化应激，并减轻 I/R 和 OGD/R 引起的内质网（ER）应激。使用 ML385（Nrf2 抑制剂）表明，OL-FS13 通过增加 Nrf2 的核移位来减轻氧化和 ER 应激引起的神经损伤。总的来说，这项研究为临床脑 I/R 治疗提供了一种新的药物候选物。
