Protective effect of Salvia Miltiorrhiza Injection on myocardial injury in rats with haemorrhagic shock resuscitated by HBOC-CHP01.

Abstract

This study investigated whether Salvia Miltiorrhiza Injection (SMI) could mitigate acute myocardial injury following resuscitation from severe haemorrhagic shock with the hemoglobin-based oxygen carrier HBOC-CHP01. Network pharmacology was first used to predict SMI's potential mechanisms. In vivo, a 50% severe haemorrhagic shock model was induced in rats, which were then resuscitated with either HBOC-CHP01 alone (n=12) or HBOC-CHP01 plus SMI (8.0 ml/kg, n=12). Subgroups were assessed for 72-hour survival, blood parameters, and myocardial tissue injury at 24 hours post-resuscitation. Network pharmacology identified 189 potential targets, with AKT1, CASP3, and HIF-1α among the core candidates. In vivo, while 72-hour survival was unchanged, SMI significantly reduced plasma cardiac injury markers (AST, LDH, CK, cTnI) at 24 hours post-resuscitation compared to HBOC-CHP01 alone. Histological analysis revealed markedly reduced myocardial inflammation and apoptosis in the SMI-treated group. This cardioprotection was associated with significant upregulation of myocardial Nrf2 and HO-1, alongside reduced reactive oxygen species and myeloperoxidase levels. In conclusion, SMI reduces myocardial injury after HBOC-CHP01 resuscitation in haemorrhagic shock rats, primarily by activating the Nrf2/HO-1 antioxidant pathway, suggesting its potential as an adjunctive therapy to improve the safety of hemoglobin-based oxygen carriers.