基于"态靶"思维的丹参红花配伍靶向P-Smad3与脑缺血再灌注损伤的相关性研究OA

Objective To investigate the protective effects of the Radix Salviae Miltiorrhizae and Flos Carthami medicinal couplet on cerebral ischemia-reperfusion injury(CIRI)and its association with P-Smad3.Methods An in vitro oxygen-glucose deprivation/reoxy-genation(OGD/R)model was established in hCMEC/d3 cells,which were divided into Control,OGD/R,DH,SIS3 HCl,and SIS3 HCl+DH groups.Cell viability,lactate dehydrogenase(LDH)release,P-Smad3 expression,and migration ability were assessed.In vivo,a middle cerebral artery occlusion(MCAO)model was induced in SD rats,which were randomized into Sham,MCAO,DH,SIS3 HCl,SIS3 HCl+DH,and Edaravone groups.Brain tissues were examined by hematoxylin-eosin staining(HE),immunohistochemistry(IHC),and Western blot(WB).Results Optimal modeling conditions were OGD for 6 h and drug concentrations of 85-680 µmol/L.Compared with the OGD/R group,the DH group showed significantly increased cell viability and migration,reduced LDH release,and elevated P-Smad3 expression,whereas SIS3 HCl exerted the opposite effects.The combination of SIS3 HCl with DH reversed the effects of SIS3 HCl alone.Consistent results were observed in vivo:MCAO rats exhibited neuronal loss,nuclear pyknosis,and elevated P-Smad3,which were alleviated by DH and Edaravone with further enhancement of P-Smad3.SIS3 HCl aggravated pathological damage and suppressed P-Smad3,while its combination with DH partially restored protective effects.Conclusion The Radix Salviae Miltiorrhi-zae and Flos Carthami medicinal couplet attenuates CIRI-induced cellular injury and enhances cell migration,potentially through nega-tive regulation of the P-Smad3 signaling pathway.