Department of Physiology, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Anatomy, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Int Immunopharmacol. 2021 Mar;92:107335. doi: 10.1016/j.intimp.2020.107335. Epub 2021 Jan 8.
Microglia/macrophages play a dual role in brain injury and repair following cerebral ischemia/reperfusion. Promoting microglia/macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype has been considered as a potential treatment for ischemic stroke. Astragaloside IV (AS-IV) is a primary active ingredient of Chinese herb Radix Astragali, which protects against acute cerebral ischemic/reperfusion injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties. However, it remains unknown whether AS-IV improves ischemic brain tissue repair and its underlying mechanism. A transient middle cerebral artery occlusion (tMCAO) rat model was used in this study. The results showed that AS-IV significantly improved long-term brain injury, reduced the expression of M1 microglia/macrophage markers and increased the expression of M2 microglia/macrophage markers 14 days after cerebral ischemia/reperfusion. AS-IV also increased peroxisome proliferator-activated receptor γ (PPARγ) mRNA and protein expression. Moreover, AS-IV promoted neurogenesis and angiogenesis, and increased the protein expression of brain-derived growth factor (BDNF), insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF). However, these beneficial effects were greatly blocked by PPARγ antagonist T0070907. These results together suggest that AS-IV could enhance neurogenesis, angiogenesis and neurological functional recovery, which may be partially through transforming microglia/macrophage from M1 to M2 phenotype in a PPARγ-dependent manner after cerebral ischemia/reperfusion injury. Therefore, AS-IV can be considered as a promising therapeutic agent for ischemic stroke.
小胶质细胞/巨噬细胞在脑缺血/再灌注后损伤和修复中起双重作用。将小胶质细胞/巨噬细胞从促炎 M1 表型极化到抗炎 M2 表型已被认为是缺血性中风的一种潜在治疗方法。黄芪甲苷（AS-IV）是中药黄芪的主要活性成分，它通过抗氧化、抗炎和抗细胞凋亡作用来保护急性脑缺血/再灌注损伤。然而，尚不清楚 AS-IV 是否改善缺血性脑组织修复及其潜在机制。本研究采用短暂性大脑中动脉闭塞（tMCAO）大鼠模型。结果表明，AS-IV 可显著改善长期脑损伤，降低脑缺血/再灌注后 14 天 M1 小胶质细胞/巨噬细胞标志物的表达，增加 M2 小胶质细胞/巨噬细胞标志物的表达。AS-IV 还增加过氧化物酶体增殖物激活受体 γ（PPARγ）mRNA 和蛋白表达。此外，AS-IV 促进神经发生和血管生成，并增加脑源性生长因子（BDNF）、胰岛素样生长因子-1（IGF-1）和血管内皮生长因子（VEGF）的蛋白表达。然而，这些有益作用被 PPARγ 拮抗剂 T0070907 大大阻断。这些结果表明，AS-IV 可增强神经发生、血管生成和神经功能恢复，这可能部分是通过在脑缺血/再灌注损伤后依赖 PPARγ 将小胶质细胞/巨噬细胞从 M1 表型转化为 M2 表型。因此，AS-IV 可被视为缺血性中风的一种有前途的治疗药物。
