Astragaloside IV promotes microglia/macrophages M2 polarization and enhances neurogenesis and angiogenesis through PPARγ pathway after cerebral ischemia/reperfusion injury in rats
Astragaloside IV promotes microglia/macrophages M2 polarization and enhances neurogenesis and angiogenesis through PPARγ pathway after cerebral ischemia/reperfusion injury in rats
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DOI：
10.1016/j.intimp.2020.107335
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发表时间：
2021-01-08
影响因子：
5.6
通讯作者：
Chu, Lisheng
中科院分区：
文献类型：
--
作者：
Li, Lin;Gan, Haiyan;Chu, Lisheng
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发挥双重作用。促进小胶质细胞/巨噬细胞从促炎性M1极化为抗炎性M2表型已被认为是缺血性卒中的潜在治疗方法。黄芪甲苷（AS-IV）是中药黄芪的主要活性成分，具有抗氧化、抗炎、抗凋亡等作用，对急性脑缺血/再灌注损伤具有保护作用。然而，AS-IV是否改善缺血脑组织修复及其潜在机制仍不清楚。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能明显改善脑缺血再灌注后的长期脑损伤，降低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（PPAR γ）mRNA和蛋白表达。此外，AS-Ⅳ还能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PPAR γ拮抗剂T0070907极大地阻断。这些结果表明，AS-IV可促进脑缺血再灌注损伤后神经发生、血管生成和神经功能恢复，其机制可能部分是通过将小胶质细胞/巨噬细胞由M1表型转化为M2表型，并以PPAR γ依赖的方式发挥作用。因此，AS-IV可以被认为是一种有前途的治疗缺血性脑卒中的药物。
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 longterm 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 gamma (PPAR gamma) mRNA and protein expression. Moreover, AS-IV promoted neurogenesis and angiogenesis, and increased the protein expression of brain-derived growth factor (BDNF), insulinlike growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF). However, these beneficial effects were greatly blocked by PPAR gamma 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 PPAR gamma-dependent manner after cerebral ischemia/ reperfusion injury. Therefore, AS-IV can be considered as a promising therapeutic agent for ischemic stroke.