Efficacy and mechanism of tenecteplase combined with butylphthalide to improve inflammatory response and neurological function in the rats with acute ischemic stroke

Chen Junjun; Zhao Zhonglin; Hou Li; Yu Yang; He Jing; Zeng Qiang

doi:10.3969/j.issn.1002-1949.2025.04.008

Abstract：Objective To explore the mechanism of tenecteplase(TNK-tPA)combined with butylphthalide to inhibit the inflammatory response and improve the neurological function in acute ischemic stroke(AIS),and to clarify the efficacy of TNK-tPA combined with butylphthalide in the treatment of AIS.Methods SD rats were used as research subjects to prepare a rat thrombotic middle cerebral artery embolism model,which was randomly divided into four groups:model group,TNK-tPA group,butylphthalide group,TNK-tPA+butylphthalide group,and six rats were set up as a sham operation group.After 24 h of modelling,depending on the grouping,TNK-tPA 1.58 mg/kg was injected into the femoral vein and(or)butylphthalide 0.7 mg/kg was given by gavage,and the rats in the sham and model groups were given an equal volume of saline,and butylphthalide was given 0.7 mg/kg by gavage for 7 days.The motor function and cognitive function tests were performed before administration,3,5 and 7 d after administration.At the end of the intervention,blood samples and brain tissue samples were taken from the rats,and 2,3,5-triphenyl tetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarction;Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and nuclear factor kappa-B(NF-κB).Results Neurological function score[(1.00±0.00)scores],locomotor score[balance bean score:(1.67±0.56)scores,rotation test:(105.00±0.00)min],cerebral infarction volume and IL-1β[(102.32±11.08)pg/mL],TNF-α[(59.76±7.78)pg/mL],NF-κB[(0.90±0.12)ng/mL]levels of rats in TNK-tPA+butylphthalide group were much better than those in model group,TNK-tPA group and butylphthalide group.Conclusions TNK-tPA combined with butylphthalide has good efficacy in the treatment of AIS,and is superior to the single one.