Department of Pharmacology, Medical School, Kunming University, Kunming, 650214, Yunnan, China.
Department of Anatomy and Histology and Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, Yunnan, China.
Biochem Biophys Res Commun. 2021 Jan 1;534:442-449. doi: 10.1016/j.bbrc.2020.11.062. Epub 2020 Nov 25.
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.
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，如何有效地预防和治疗缺血性脑卒中已成为近年来的研究热点。在这里，我们鉴定了一种新型多肽，命名为 HsTx2（AGKKERAGSRRTKIVMLKCIREHGH，2 861.855 Da），来源于蝎子 Heterometrus spinifer，它在缺血性脑卒中大鼠中表现出明显的抗中风作用。结果进一步表明，HsTx2 可显著减少梗死面积的形成，并改善缺血性脑卒中大鼠的行为异常。这些保护作用可能是通过激活丝裂原活化蛋白激酶（MAPK）信号通路发挥的，即在大鼠大脑皮层和激活的小胶质细胞（AM）中上调磷酸化 ERK1/2；在大脑皮层中上调磷酸化 p38（p-p38）；并抑制 AM 中磷酸化 JNK 和 p-p38 的水平。总之，本研究强调 HsTx2 可能是一种潜在的脑卒中神经保护剂。
