Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
PLoS One. 2019 Jan 15;14(1):e0209184. doi: 10.1371/journal.pone.0209184. eCollection 2019.
Ischemic stroke is one of the most common causes of death worldwide and is a major cause of acquired disability in adults. However, there is still a need for an effective drug for its treatment. Buyang Huanwu decoction (BHD), a traditional Chinese medicine (TCM) prescription, has long been used clinically to aid neurological recovery after stroke. To establish potential clinical indicators of BHD efficacy in stroke treatment and prognosis, we conducted a combined proteomic and metabolomic analysis of cerebrospinal fluid (CSF) samples in a mouse stroke model. CSF samples were obtained from male mice with acute ischemic stroke induced by middle cerebral ischemic/reperfusion (CI/R) injury, some of which were then treated with BHD. Label-free quantitative proteomics was conducted using nano-LC-MS/MS on an LTQ Orbitrap mass and metabolomic analysis was performed using nanoprobe NMR and UHPLC-QTOF-MS. The results showed that several proteins and metabolites were present at significantly different concentrations in the CSF samples from mice with CI/R alone and those treated with BHD. These belonged to pathways related to energy demand, inflammatory signaling, cytoskeletal regulation, Wnt signaling, and neuroprotection against neurodegenerative diseases. In conclusion, our in silico data suggest that BHD treatment is not only protective but can also ameliorate defects in pathways affected by neurological disorders. These data shed light on the mechanism whereby BHD may be effective in the treatment and prevention of stroke-related neurodegenerative disease.
缺血性脑卒中是全球范围内最常见的死亡原因之一，也是成年人获得性残疾的主要原因。然而，目前仍需要一种有效的药物来治疗这种疾病。补阳还五汤（BHD）是一种中药方剂，长期以来一直被临床用于辅助脑卒中后的神经功能恢复。为了确定 BHD 在脑卒中治疗和预后中的潜在临床疗效指标，我们对大脑中动脉缺血/再灌注（CI/R）损伤诱导的雄性小鼠脑卒中模型的脑脊液（CSF）样本进行了蛋白质组学和代谢组学联合分析。从急性缺血性脑卒中的小鼠中获得 CSF 样本，其中一些样本用 BHD 进行了处理。使用 LTQ Orbitrap 质谱仪的纳升 LC-MS/MS 进行无标记定量蛋白质组学分析，使用纳米探针 NMR 和 UHPLC-QTOF-MS 进行代谢组学分析。结果表明，CI/R 单独处理和 BHD 处理的小鼠 CSF 样本中的几种蛋白质和代谢物的浓度存在显著差异。这些蛋白质和代谢物属于与能量需求、炎症信号、细胞骨架调节、Wnt 信号和神经退行性疾病的神经保护相关的途径。总之，我们的计算机数据表明，BHD 治疗不仅具有保护作用，而且可以改善受神经紊乱影响的途径的缺陷。这些数据揭示了 BHD 可能在治疗和预防与脑卒中相关的神经退行性疾病方面有效的机制。
