丹参-红花调节TGF-β1/Smad3-ICAM1轴对脑缺血血管稳态的影响OA

Objective To investigate the effect and mechanism of the combined active components of Radix Salviae Miltiorrhizae and Flos Carthami on vascular homeostasis after cerebral ischemia-reperfusion injury(CIRI).Methods In vitro,an oxygen-glucose depriva-tion/reperfusion(OGD/R)model was established in hCMEC/d3 cells,divided into Control,OGD/R,DH,SIS3 Hcl,and SIS3 Hcl+DH groups.Levels of transforming growth factor-β1(TGF-β1)and intercellular adhesion molecule-1(ICAM1)were detected.In vivo,a middle cerebral artery occlusion(MCAO)model was established in SD rats,divided into Sham,MCAO,DH,SIS3 Hcl,SIS3 Hcl+DH,and Positive groups.Neurological function scores were assessed.Serum levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were measured.The protein and mRNA expression of Smad3 and ICAM1 in brain tissue was analyzed by immunohistochemistry(IHC),reverse transcription quantitative polymerase chain reaction(RT-qPCR),and Western blot(WB).Results OGD/R significantly increased TGF-β1 and ICAM1 levels.DH treatment further upregulated TGF-β1 and downregulated ICAM1,while SIS3 Hcl inhibited TGF-β1 and elevated ICAM1.Co-treatment with DH reversed these effects.In MCAO rats,neurological function scores,inflammatory factors(TNF-α,IL-1β),and expression of Smad3 and ICAM1 in brain tissue were significantly increased.Both the DH and Positive groups reduced inflammatory responses and ICAM1 expression while increasing Smad3 levels.SIS3 Hcl aggravated the inflammatory response and downregulated Smad3,whereas its combination with DH ameliorated the injury and restored vascular homeostasis.Conclu-sion The combination of active components from Radix Salviae Miltiorrhizae and Flos Carthami can alleviate vascular inflammation,maintain vascular homeostasis,and protect brain tissue after CIRI,potentially by regulating the TGF-β1/Smad3 signaling pathway.