School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
School of Basic Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Int J Mol Sci. 2023 Jan 21;24(3):2126. doi: 10.3390/ijms24032126.
Promotion of angiogenesis and restoration of the blood flow in the ischemic penumbra is an effective treatment for patients with ischemic stroke (IS). Radix astragali-safflower (AS), a classic herbal pair for accelerating blood circulation and dispersing blood stasis, has been used for thousands of years to treat patients with IS in China. Even so, the mechanism of the treatment of IS by AS is still undecipherable. In the current study, network pharmacology was firstly employed to unveil the mechanism of AS in treating IS, which showed that AS might promote angiogenesis associated with PTGS2 silence. Middle cerebral artery occlusion/reperfusion (MCAO/R) model rats were then used as the experimental animals to verify the prediction result. The experimental results revealed that treatment with AS improved the cerebral infarct volume, neurological damage, and cerebral histopathological damage; inhibited cell apoptosis; increased the contents of PDGF-BB, EPO, and TGF-β1; and reduced the levels of PF4, Ang-2, and TIMP-1 in serum. Immunohistochemical staining demonstrated that the expression of PTGS2 was dramatically increased in the hippocampus and cerebral cortex of rats with MCAO/R, and this trend was reversed by the treatment of AS. Immunofluorescent staining expressed that AS reversed the down-regulation of VEGF and further promoted the expression of CD31, which indicated that AS promoted angiogenesis in MCAO/R rats. The abnormal protein or mRNA expression of PTGS2, PGI2, bFGF, TSP-1, and VEGF in the penumbra were transposed by AS or Celecoxib (an inhibitor of PTGS2). In conclusion, the protective mechanism of AS for IS promoted angiogenesis and was involved with PTGS2 silence.
促进血管生成和恢复缺血半影区的血流是治疗缺血性中风（IS）患者的有效方法。黄芪红花（AS）是一种经典的活血化瘀药对，在中国已使用数千年治疗 IS 患者。即便如此，AS 治疗 IS 的机制仍未被破译。在本研究中，首先采用网络药理学揭示 AS 治疗 IS 的作用机制，表明 AS 可能通过沉默 PTGS2 促进血管生成。然后，使用大脑中动脉闭塞/再灌注（MCAO/R）模型大鼠作为实验动物来验证预测结果。实验结果表明，AS 治疗可改善脑梗死体积、神经损伤和脑组织病理学损伤；抑制细胞凋亡；增加 PDGF-BB、EPO 和 TGF-β1 的含量；并降低血清中 PF4、Ang-2 和 TIMP-1 的水平。免疫组织化学染色显示，MCAO/R 大鼠海马和大脑皮质中 PTGS2 的表达明显增加，AS 治疗可逆转这种趋势。免疫荧光染色显示，AS 逆转了 VEGF 的下调，并进一步促进了 CD31 的表达，表明 AS 促进了 MCAO/R 大鼠的血管生成。AS 或塞来昔布（PTGS2 抑制剂）可使缺血半影区中 PTGS2、PGI2、bFGF、TSP-1 和 VEGF 的异常蛋白或 mRNA 表达发生转位。总之，AS 对 IS 的保护作用机制促进了血管生成，并涉及到 PTGS2 的沉默。
