Buyang Huanwu decoction promotes angiogenesis of rat brain microvascular endothelial cells after oxygen-glucose deprivation reperfusion injury via activation of PI3K-AKT signaling pathway

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2022 Nov 25;51(5):544-551. doi: 10.3724/zdxbyxb-2022-0324.

Abstract

Objective: To investigate the effect and mechanism of Buyang Huanwu decoction (BYHWD) on angiogenesis of rat brain microvascular endothelial cells (RBMECs) after oxygen-glucose deprivation reperfusion (OGD/R) injury.

Methods: RBMECs were pretreated with BYHWD containing serum 24 h before OGD/R injury was induced. Cells were randomly divided into blank control group, model control group, BYHWD group (provided BYHWD containing serum) and LY294002 group [treated with phosphoinositide 3-kinase (PI3K) inhibitor LY294002 for 1 h before provided BYHWD containing serum]. The cell viability, migration and tube formation abilities of RBMECs were detected by CCK-8, scratch wound healing, Transwell migration and tube formation assays, respectively. The protein expression levels of PI3K, p-PI3K, protein kinase B (AKT), p-AKT, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were determined by Western blotting.

Results: Compared with model control group, cell viability, migration and tube formation abilities of RBMECs were significantly improved in BYHWD group (all P<0.01), the protein expression levels of p-PI3K, p-AKT, HIF-1α and VEGF were up-regulated (all P<0.05); while above effects were blocked by LY294002.

Conclusion: BYHWD can promote angiogenesis of RBMECs after OGD/R injury, which may be related to the increased protein expression of HIF-1α and VEGF through activation of PI3K-AKT signaling pathway.

Keywords: Angiogenesis; Brain microvascular endothelial cells; Buyang Huanwu decoction; Hypoxia-inducible factor-1α; Oxygen- glucose deprivation reperfusion; PI3K-AKT signaling pathway; Vascular endothelial growth factor.

MeSH terms

  • Animals
  • Brain / metabolism
  • Endothelial Cells / metabolism
  • Glucose / metabolism
  • Glucose / pharmacology
  • Oxygen / metabolism
  • Phosphatidylinositol 3-Kinase* / metabolism
  • Phosphatidylinositol 3-Kinase* / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Reperfusion Injury*
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • buyang huanwu
  • Phosphatidylinositol 3-Kinase
  • Phosphatidylinositol 3-Kinases
  • Vascular Endothelial Growth Factor A
  • Proto-Oncogene Proteins c-akt
  • Oxygen
  • Glucose

Grants and funding

国家自然科学基金(81073075); 浙江省自然科学基金(LY22H280009); 浙江中医药大学校级科研基金项目(2019ZY20,2021JKZC01)