School of Traditional Chinese Medicine, Capital Medical University, Beijing, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing, China.
Medical Imaging Laboratory of Core Facility Center, Capital Medical University, Beijing, China.
Phytomedicine. 2024 Dec;135:156096. doi: 10.1016/j.phymed.2024.156096. Epub 2024 Sep 27.
Trillium tschonoskii rhizome saponins (TSTT) has been significantly effective in treating traumatic injury, neurasthenia, cancer and inflammatory diseases as a folk medicine. However, the mechanism regarding to TSTT induced the neurovascular restorative after ischemia is without fully elucidated.
This research was constructed to study the value of TSTT in promoting endogenous repair of neurovascular and augmenting the ability of spatial study and memory retention in ischaemic rats.
The improvement of TSTT on cerebral infraction and perfusion was observed by magnetic resonance imaging (MRI) experiments and the molecular mechanisms were further explored.
First, rats were ligated the middle cerebral artery to construct a permanent ischaemia model, subsequently intragastric injection administrated with TSTT (120, 60, 30 mg kg) at 6 h after operation, then once a day during next 30 days. Morris water maze was applied to observe the neurobehavioral changes. Multimodal MRI sequences were performed to monitoring brain injuries as well as cerebral blood flow. Histopathological staining was employed to evaluate the morphological changes of neurons. Transmission electron microscopy (TEM) was employed to detect the neurons, vascular structure, and synapse. Immunofluorescent staining was utilized to evaluate the endogenous repair progress. The axonal growth-inhibitors and axonal guidance cues were analyzed using western blotting.
Contrast to the model group, TSTT declined the infarction and elevated the parenchymal volume. Notably, treated with TSTT significantly decreased the ADC (ipsilateral/contralateral). In histopathologic examination, TSTT prominently boosted amounts of cortical and striatal nerve cells and protected ultrastructure of neurovascular unit. According with results of nuclear magnetic imaging, TSTT enhanced endogenous repair progress. Especially, TSTT treatments obviously inhibited protein levels of NogoA/NgR/RhoA/ROCK2, accompanied by increased expression of Netrin/DCC and Slit2/Robo1.
To sum up, our data illustrated that TSTT promoted cerebral reestablishment. The above result was in line with improving cerebral blood flow, elevated integrity of neurovascular structure, accelerating endogenous restoration and impairing the axonal growth inhibitors NogoA/NgR/RhoA/ROCK2 signaling, thereby improving poststroke learning and memory.
作为一种民间药物，延龄草根茎皂甙（TSTT）在治疗创伤、神经衰弱、癌症和炎症性疾病方面具有显著疗效。然而，关于 TSTT 诱导缺血后神经血管修复的机制尚未完全阐明。
本研究旨在探讨 TSTT 在促进神经血管内源性修复和增强缺血大鼠空间学习记忆保留能力方面的价值。
通过磁共振成像（MRI）实验观察 TSTT 对脑梗死和灌注的改善，并进一步探讨其分子机制。
首先，通过结扎大脑中动脉构建永久性缺血模型，然后在术后 6 小时给予 TSTT（120、60、30mg/kg）灌胃，每天一次，共 30 天。应用 Morris 水迷宫观察神经行为变化。采用多模态 MRI 序列监测脑损伤和脑血流。组织病理学染色评估神经元形态变化。透射电镜（TEM）观察神经元、血管结构和突触。免疫荧光染色评估内源性修复进展。采用 Western blot 分析轴突生长抑制因子和轴突导向因子。
与模型组相比，TSTT 降低了梗死面积，增加了实质体积。值得注意的是，TSTT 显著降低了 ADC（同侧/对侧）。组织病理学检查显示，TSTT 明显增加了皮质和纹状体神经细胞的数量，并保护了神经血管单元的超微结构。与磁共振成像结果一致，TSTT 增强了内源性修复过程。特别是，TSTT 处理明显抑制了 NogoA/NgR/RhoA/ROCK2 蛋白水平，同时增加了 Netrin/DCC 和 Slit2/Robo1 的表达。
综上所述，我们的数据表明 TSTT 促进了脑重建。上述结果与改善脑血流、提高神经血管结构完整性、加速内源性修复以及抑制轴突生长抑制因子 NogoA/NgR/RhoA/ROCK2 信号有关，从而改善了卒中后学习和记忆能力。
