丹参注射液对HBOC-CHP01复苏失血性休克大鼠心肌损伤的保护作用

摘要(中文译文)

本研究探讨了丹参注射液（SMI）能否减轻以血红蛋白类氧载体HBOC-CHP01复苏严重失血性休克后的急性心肌损伤。首先采用网络药理学预测SMI的潜在机制。在体内实验中，建立大鼠50%严重失血性休克模型，随后分别单独使用HBOC-CHP01（n=12）或HBOC-CHP01联合SMI（8.0 ml/kg，n=12）进行复苏。对各亚组评估72小时生存率、血液参数及复苏后24小时的心肌组织损伤。网络药理学鉴定出189个潜在靶点，其中AKT1、CASP3和HIF-1α为核心候选靶点。在体内实验中，虽然72小时生存率无变化，但与单独使用HBOC-CHP01相比，SMI显著降低了复苏后24小时的血浆心肌损伤标志物（AST、LDH、CK、cTnI）。组织学分析显示，SMI治疗组心肌炎症和凋亡明显减轻。这种心脏保护作用与心肌Nrf2和HO-1的显著上调以及活性氧和髓过氧化物酶水平的降低相关。总之，SMI可减轻失血性休克大鼠HBOC-CHP01复苏后的心肌损伤，主要通过激活Nrf2/HO-1抗氧化通路，提示其作为辅助治疗以提高血红蛋白类氧载体安全性的潜力。

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.

如何引用