当前位置: X-MOL 学术Int. Immunopharmacol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Astragaloside IV promotes microglia/macrophages M2 polarization and enhances neurogenesis and angiogenesis through PPARγ pathway after cerebral ischemia/reperfusion injury in rats
International Immunopharmacology ( IF 4.8 ) Pub Date : 2021-01-08 , DOI: 10.1016/j.intimp.2020.107335
Lin Li 1 , Haiyan Gan 1 , Huaqian Jin 1 , Yan Fang 1 , Yan Yang 1 , Jianping Zhang 2 , Xiaowei Hu 1 , Lisheng Chu 1
Affiliation  

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.



中文翻译:

黄芪甲苷IV促进大鼠脑缺血/再灌注损伤后小胶质细胞/巨噬细胞M2极化,并通过PPARγ途径增强神经发生和血管生成。

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。

更新日期:2021-01-08
down
wechat
bug