关键词: 川芎嗪, miR-497-5p, 表皮生长因子样蛋白7, 血管生成, 脊髓损伤, 神经再生

Abstract: Objective　To explore the protective effect of tetramethylpyrazine (TMP) on vascular endothelium and nerves in rats with spinal cord injury (SCI), and to analyze its mechanism of action in the treatment of SCI based on the miR-497-5p/EGFL7 axis.Methods　A total of 78 healthy male SD rats were randomly grouped into 13 groups, with 6 rats in each group. The SCI rat model was constructed by the modified Allen method, and then TMP intervention was continuously given for 2 weeks. The expression levels of miR-497-5p and epidermal growth-like protein 7 (EGFL7) were detected by RT qPCR and Western blot. Meanwhile, Basso, Beattie and Bresnahan (BBB) scoring, footprint analysis,  HE staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, enzyme linked immunosorbent assay (ELISA), dual-luciferase reporter assay and in vivo gene regulation experiments were employed. A comprehensive evaluation was conducted on indicators such as motor function, spinal cord tissue injury, apoptosis, inflammatory response and angiogenesis in rats.Results After SCI,the expression of miR-497-5p in the spinal cord tissue of rats was significantly increased, and the expression of EGFL7 was significantly decreased. At the same time, it was accompanied by typical manifestations such as motor dysfunction, tissue structure destruction, increased apoptosis and elevated levels of inflammatory factors. After TMP intervention, the above-mentioned abnormal changes were significantly improved. Specifically, the expression of miR-497-5p was down-regulated, the expression of EGFL7 was up-regulated, the BBB score and footprint analysis indicators were improved, the degree of pathological damage and apoptosis was reduced, and the expression of platelet endothelial cell adhesion molecule-1 (CD31) was increased. The levels of tumor necrosis factor -α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin-1 β (IL-1β) decreased.Conclusion　TMP improves the local microenvironment following SCI by regulating the miR-497-5p/EGFL7 axis, thereby promoting angiogenesis and neural repair. Downregulation of miR-497-5p or upregulation of EGFL7 enhances its protective effects, whereas their opposite regulation attenuates these effects.

Key words: tetramethylpyrazine, miR-497-5p, EGFL7, angiogenesis, spinal cord injury, neural regeneration