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/再灌注后的脑损伤和修复中起双重作用。将小胶质细胞/巨噬细胞极化从促炎性M1转变为消炎M2表型已被认为是缺血性卒中的潜在治疗方法。黄芪甲苷IV（AS-IV）是中草药黄芪的主要活性成分，具有抗氧化，抗炎和抗凋亡的作用，可预防急性脑缺血/再灌注损伤。但是，尚不清楚AS-IV是否改善缺血性脑组织修复及其潜在机制。在本研究中使用了短暂性脑中动脉阻塞（tMCAO）大鼠模型。结果表明，AS-IV可显着改善长期脑损伤，降低脑缺血/再灌注后14天的M1小胶质细胞/巨噬细胞标志物的表达，并增加M2小胶质细胞/巨噬细胞标志物的表达。AS-IV还增加了过氧化物酶体增殖物激活的受体γ（PPARγ）mRNA和蛋白质表达。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）的蛋白质表达。但是，PPARγ拮抗剂T0070907大大阻止了这些有益作用。这些结果共同表明，AS-IV可以增强神经发生，血管生成和神经功能恢复，这可能部分是通过在脑缺血/再灌注损伤后以PPARγ依赖性方式将小胶质细胞/巨噬细胞从M1表型转变为M2表型。