Yang Le, Lei Jian-Feng, Ouyang Jun-Yao, Li Man-Zhong, Zhan Yu, Feng Xue-Feng, Lu Yun, Li Ming-Cong, Wang Lei, Zou Hai-Yan, Zhao Hui
School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing, China.
Front Pharmacol. 2021 Dec 10;12:763181. doi: 10.3389/fphar.2021.763181. eCollection 2021.
Maxim. (TTM), is a perennial herb from Liliaceae, that has been widely used as a traditional Chinese medicine treating cephalgia and traumatic hemorrhage. The present work was designed to investigate whether the total saponins from Maxim. (TSTT) would promote brain remodeling and improve gait impairment in the chronic phase of ischemic stroke. A focal ischemic model of male Sprague-Dawley (SD) rats was established by permanent middle cerebral artery occlusion (MCAO). Six hours later, rats were intragastrically treated with TSTT (120, 60, and 30 mg/kg) and once daily up to day 30. The gait changes were assessed by the CatWalk-automated gait analysis system. The brain tissues injuries, cerebral perfusion and changes of axonal microstructures were detected by multimodal magnetic resonance imaging (MRI), followed by histological examinations. The axonal regeneration related signaling pathways including phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3)/collapsin response mediator protein-2 (CRMP-2) were measured by western blotting. TSTT treatment significantly improved gait impairment of rats. MRI analysis revealed that TSTT alleviated tissues injuries, significantly improved cerebral blood flow (CBF), enhanced microstructural integrity of axon and myelin sheath in the ipsilesional sensorimotor cortex and internal capsule. In parallel to MRI findings, TSTT preserved myelinated axons and promoted oligodendrogenesis. Specifically, TSTT interventions markedly up-regulated expression of phosphorylated GSK-3, accompanied by increased expression of phosphorylated PI3K, AKT, but reduced phosphorylated CRMP-2 expression. Taken together, our results suggested that TSTT facilitated brain remodeling. This correlated with improving CBF, encouraging reorganization of axonal microstructure, promoting oligodendrogenesis and activating PI3K/AKT/GSK-3/CRMP-2 signaling, thereby improving poststroke gait impairments.
绵枣儿（TTM）是百合科多年生草本植物，作为治疗头痛和创伤性出血的传统中药被广泛使用。本研究旨在探讨绵枣儿总皂苷（TSTT）是否能促进脑重塑并改善缺血性中风慢性期的步态障碍。通过永久性大脑中动脉闭塞（MCAO）建立雄性Sprague-Dawley（SD）大鼠局灶性缺血模型。6小时后，大鼠灌胃给予TSTT（120、60和30mg/kg），每天一次，持续至第30天。通过CatWalk自动步态分析系统评估步态变化。通过多模态磁共振成像（MRI）检测脑组织损伤、脑灌注和轴突微观结构变化，随后进行组织学检查。通过蛋白质印迹法检测轴突再生相关信号通路，包括磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/糖原合酶激酶-3（GSK-3）/塌陷反应调节蛋白-2（CRMP-2）。TSTT治疗显著改善了大鼠的步态障碍。MRI分析显示，TSTT减轻了组织损伤，显著改善了脑血流量（CBF），增强了同侧感觉运动皮层和内囊轴突和髓鞘的微观结构完整性。与MRI结果一致，TSTT保留了有髓轴突并促进了少突胶质细胞生成。具体而言，TSTT干预显著上调了磷酸化GSK-3的表达，同时磷酸化PI3K、AKT的表达增加，但磷酸化CRMP-2的表达降低。综上所述，我们的结果表明TSTT促进了脑重塑。这与改善CBF、促进轴突微观结构重组、促进少突胶质细胞生成和激活PI3K/AKT/GSK-3/CRMP-2信号传导相关联，从而改善中风后的步态障碍。
