Promotion of angiogenesis in cerebral infarction by Tongqiao Huoxue Decoction through activation of glycolysis

Angiogenesis plays a critical role in mitigating cerebral infarction injury. However, both endogenous and exogenous angiogenic responses are often insufficient to generate stable, functional blood vessels. Brain microvascular endothelial cells rely primarily on glycolysis for energy, a process that intensifies under hypoxic conditions. Therefore, enhancing energy metabolism may support angiogenesis. Tongqiao Huoxue Decoction (TQHXD) has been shown to have therapeutic effects on cerebral infarction, but its ability to promote angiogenesis by enhancing glycolysis remains unclear. We established an in vivo middle cerebral artery occlusion (MCAO) model and analyzed four postinfarction stages: hyperacute, acute, subacute and chronic. Brain injury in MCAO rats was assessed using neurobehavioral scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin‒eosin (HE) staining, and brain water content measurements. The relationship between angiogenesis and glycolysis was further evaluated using enzyme-linked immunosorbent assays (ELISAs), western blotting (WB), reverse transcription polymerase chain reaction (RT‒PCR), and immunohistochemistry (IHC). TQHXD significantly alleviated brain injury and improved neurological function in MCAO rats. Treatment with TQHXD markedly increased the expressions of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), which are potentially linked to elevated levels of glucose, pyruvate, lactate, glucose transporter 1 (GLUT1), phosphofructokinase (PFK), and Lactate Dehydrogenase A (LDHA). Therefore, in the early stages of cerebral infarction (hyperacute and acute stages), TQHXD activates the HIF-1α/VEGF pathway by enhancing glycolysis, thereby accelerating the formation of new blood vessels and inhibiting cerebral infarction damage.

Angiogenesis; Cerebral infarction; Energy metabolism; Glycolysis; HIF-1/VEGF; Tongqiao Huoxue decoction.