Med Sci Monit. 2026 Aug 27;32:e953474. doi: 10.12659/MSM.953474.
ABSTRACT
BACKGROUND Ischemic stroke causes severe neurological damage, and promoting angiogenesis in the ischemic penumbra is critical for neurovascular reconstruction and functional recovery. Astragaloside IV (AS-IV) and Tetramethylpyrazine (TMP) are a classic Chinese medicine combination for treating ischemic stroke, yet their synergistic mechanisms are unclear. This study aimed to investigate the enhanced effects of AS-IV combined with TMP on cerebral microvascular endothelial cells following ischemia-reperfusion injury and to explore the regulatory role of the lncRNA MALAT1-CXCL12/CXCR4 signaling axis. MATERIAL AND METHODS An oxygen-glucose deprivation/reperfusion (OGD/R) model was established using the bEnd.3 mouse brain microvascular endothelial cell line. Cells were treated with AS-IV, TMP, or their combination to evaluate therapeutic efficacy. Cell viability and migration capacity were assessed using CCK-8, wound healing, and Transwell assays. The expression levels of MALAT1 and angiogenesis-related markers (VEGFA, Ang1, Ang2, CXCL12, and CXCR4) were analyzed via qPCR, western blot, and immunofluorescence. To verify the mechanism, a stable MALAT1 knockdown model was constructed using lentiviral-mediated shRNA transduction. RESULTS OGD/R insult significantly reduced cell viability and migration, downregulated MALAT1 expression, and disrupted the Ang1/Ang2 balance. While AS-IV or TMP monotherapy partially mitigated these injuries, the combined treatment demonstrated a greater protective effect than either monotherapy. This enhancement was characterized by upregulation of MALAT1, activation of the CXCL12/CXCR4 pathway, and restoration of VEGFA and Ang1 protein expression. Furthermore, lentiviral-mediated MALAT1 silencing (shMALAT1) markedly impaired cell migration and angiogenic marker expression, effects that were partially rescued by the combined AS-IV and TMP intervention. CONCLUSIONS The combination of AS-IV and TMP exhibits an enhanced effect compared to either monotherapy in promoting endothelial migration and marker expression in vitro. These findings suggest that the protective mechanism is consistent with the involvement of the MALAT1-CXCL12/CXCR4 signaling axis. This study provides a preliminary cellular rationale for further in vivo validation of this combination therapy in rodent stroke models.
PMID:42655892 | DOI:10.12659/MSM.953474