School of Biology and Basic Medical Science, Soochow University, Suzhou, China; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Brain Res. 2019 Mar 1;1706:166-176. doi: 10.1016/j.brainres.2018.11.010. Epub 2018 Nov 8.
Achyranthes bidentata Bl. (A. bidentata) occupies an important position in traditional Chinese medicine owing to the property of promoting the circulation of blood and removing stasis. Achyranthes bidentata polypeptide k (ABPPk) is one of the active components isolated from A. bidentata. We previously demonstrated that ABPPk has potent neuroprotective effects against neuronal apoptosis both in vitro and in vivo, but the roles and mechanisms of ABPPk on long-term functional recovery after ischemic stroke remain unknown. In the current study, we investigated the neuroprotective effects of ABPPk on filament transient middle cerebral artery occlusion (tMCAO) rats and found that ABPPk reduced the infarct volume and maintained the neuronal integrity in the ischemic penumbra. Moreover, we found that ABPPk might reduce the formation of downstream microthrombus through preventing ischemic-induced oxidative damage of brain endothelial cells and activation of tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), and NF-κB. ABPPk also inhibited polymorphonuclear leukocytes (PMNs) infiltration and matrix metalloproteinase-2/-9 (MMP-2/-9) activation in the ischemic penumbra. Morris water maze, foot fault test, and modified neurological severity score were assessed for a period of 6 weeks following tMCAO. ABPPk improved long-term recognition abilities and neurological outcomes after stroke compared with saline-treated rats. Taken together, these results suggested that ABPPk is beneficial to the improvement of long-term outcomes after transient cerebral ischemia injury and can be used as a potential neuroprotective agent.
牛膝（Achyranthes bidentata Bl.）因其具有活血化瘀的功效而在中药中占有重要地位。牛膝多肽 k（ABPPk）是从牛膝中分离得到的一种活性成分。我们之前的研究表明，ABPPk 在体外和体内均对神经元凋亡具有很强的神经保护作用，但 ABPPk 对缺血性中风后长期功能恢复的作用和机制尚不清楚。在本研究中，我们研究了 ABPPk 对线栓短暂性大脑中动脉阻塞（tMCAO）大鼠的神经保护作用，发现 ABPPk 可减少梗死体积并维持缺血半影区神经元的完整性。此外，我们发现 ABPPk 可能通过防止脑内皮细胞缺血诱导的氧化损伤和组织因子（TF）、纤溶酶原激活物抑制剂-1（PAI-1）和 NF-κB 的激活，减少下游微血栓的形成。ABPPk 还抑制缺血半影区中性粒细胞（PMNs）浸润和基质金属蛋白酶-2/-9（MMP-2/-9）的激活。tMCAO 后 6 周内通过 Morris 水迷宫、足误试验和改良神经功能严重程度评分进行评估。与盐水处理的大鼠相比，ABPPk 改善了中风后的长期认知能力和神经功能结局。综上所述，这些结果表明 ABPPk 有利于改善短暂性脑缺血损伤后的长期结局，可以作为一种潜在的神经保护剂。
