研究领域：神经科学 药理学 分子生物学

关键字：HsTx2 蝎毒肽 缺血性中风 MAPK信号通路 大鼠模型 神经保护

缺血性脑卒中因其高复发率、高死亡率和高致残率，严重威胁人类健康。因此，如何有效预防和治疗缺血性脑卒中已成为近年来的研究热点。本研究从蝎子 Heterometrus spinifer 中鉴定出一种新型多肽，命名为 HsTx2（序列：AGKKERAGSRRTKIVMLKCIREHGH，分子量：2 861.855 Da），该多肽在缺血性脑卒中大鼠模型中表现出显著的抗脑卒中作用。进一步结果表明，HsTx2 可显著减少脑梗死面积，并改善缺血性脑卒中大鼠的行为学异常。这些神经保护作用可能通过激活丝裂原活化蛋白激酶（MAPK）信号通路介导：即上调大鼠大脑皮层及活化小胶质细胞（AM）中磷酸化 ERK1/2（p-ERK1/2）的表达；上调大脑皮层中磷酸化 p38（p-p38）的表达；同时抑制 AM 中磷酸化 JNK（p-JNK）和 p-p38 的表达水平。综上所述，本研究提示 HsTx2 是一种具有潜力的脑卒中神经保护剂。Ischemic stroke is a severe threat to human health due to its high recurrence, mortality, and disability rates. As such, how to prevent and treat ischemic stroke effectively has become a research hotspot in recent years. Here, we identified a novel peptide, named HsTx2 (AGKKERAGSRRTKIVMLKCIREHGH, 2 861.855 Da), derived from the scorpion Heterometrus spinifer , which showed obvious anti-apoplectic effects in rats with ischemic stroke. Results further demonstrated that HsTx2 significantly reduced formation of infarct area and improved behavioral abnormalities in ischemic stroke rats. These protective effects were likely exerted via activation of the mitogen-activated protein kinase (MAPK) signaling pathway , i.e., up-regulation of phosphorylated ERK1/2 in both rat cerebral cortex and activated microglia (AM); up-regulation of phosphorylated p38 (p-p38) in the cerebral cortex; and inhibition of phosphorylated JNK and p-p38 levels in the AM. In conclusion, this study highlights HsTx2 as a potential neuroprotective agent for stroke.