[Dual regulatory mechanisms of hemostasis and promotion of blood circulation of Shangke Jiegu Tablets in fracture healing based on gene interaction and dynamic expression profiles].

This study aimed to integrate the gene interaction profiles and dynamic expression profiles associated with blood microcirculation at fracture sites, in order to explore the molecular mechanism underlying the dual regulatory effects of Shangke Jiegu Tablets on hemostasis and activation of blood circulation in promoting fracture healing. The candidate target profiles of Shangke Jiegu Tablets were retrieved from the ETCM 2.0 and HIT 2.0 databases, while the targets related to hemostasis and promotion of blood circulation were obtained from the HPO database. An interaction network of "herbal medicine candidate targets-hemostasis/promotion of blood circulation-related targets" was constructed, and the key network targets were identified for functional enrichment analysis. Gene sets showing dynamic changes over time during the fracture-healing process were retrieved from the GEO database and correlated with the key targets related to hemostasis and the promotion of blood circulation of Shangke Jiegu Tablets. Independent transcriptomic quantitative datasets and animal experiments were employed to validate the associated targets. Correlation analysis reveals that during the hematoma formation stage, Shangke Jiegu Tablets effectively promoted hemostasis at the fracture site by upregulating the expression of decay-accelerating factor(DAF, also known as CD55). During the callus formation and remodeling stages, it promoted blood circulation by downregulating interleukin-6(IL-6) and upregulating plasminogen activator urokinase(PLAU). Animal experiments demonstrated that Shangke Jiegu Tablets significantly increased the bone volume fraction(bone volume/total volume, BV/TV) and trabecular thickness(Tb.Th) in fractured rats and shortened the recovery period of abnormal CD55, IL-6, and PLAU expression, with statistically significant differences compared with the fracture model group. At different stages of fracture healing, Shangke Jiegu Tablets can effectively regulate the complement and coagulation cascade pathways involving CD55 and PLAU, as well as the hematopoietic cell function pathway involving CD55 and IL-6. This modulation enables the drug to exert its dual regulatory effects on blood microcirculation at the fracture site, providing a novel perspective on the therapeutic mechanism of Shangke Jiegu Tablets for fracture treatment.