Neuroprotective Effect and Mechanism of Astragaloside IV and Tanshinone IIA on Rats with Ischemic Stroke

SHI Yuanyuan; FU Dewang

doi:10.3969/j.issn.2096-305X.2025.01.006

Abstract：Objective To investigate the neuroprotective effect and mechanism of astragaloside IV(AS-IV)combined with tanshinone IIA(Ta-IIA)on ischemic stroke rats.Methods A model of middle cerebral artery occlusion(line plug method)was established,and oxygen glucose deprivation(OGD)method was used to simulate the hypoxia and glucose deficiency environment in vitro.SD rats were divided into three groups,sham group,model group,and AS-IV+Ta-IIA(20 in each group).After administration,neurological deficits were assessed by Zea-Longa score.The grip strength test was used to evaluate the grip time of rats.Infarct volume and brain tissue water content detection method were used to observe brain tissue infarction and edema;the Cell Counting Kit-8(CCK-8)experiment was used to screen out the optimal combined administration concentration;enzyme-linked immunosorbent assay was used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-10(IL-10)and interleukin(IL-1β);real-time quantitative PCR(qRT-PCR)was used to detect the changes of Nuclear factor erythroid 2-related factor 2(Nrf2)and Heme oxygenase 1(HO-1)in rat brain tissue;immunofluorescence was used to detect the expression level of Cleaved-Caspase 3(CC3)in brain tissue and neuronal cells.Results The neurological function score,cerebral infarction volume,cerebral edema,malondialdehyde(malondialdehyde,MDA),NO,TNF-α,and interleukin 1β(IL-1β),HO-1 mRNA,Nrf2 mRNA,and CC3 were significantly increased compared with the sham group(P<0.05);grip strength,IL-10,GSH,and SOD were significantly decreased(P<0.05).Compared with the model group,neurological function score,cerebral infarction volume,cerebral edema,MDA,and NO,TNF-α and IL-1 β,CC3 expression levels decreased(P<0.05);grip strength,IL-10,GSH,SOD,and HO-1 mRNA levels increased significantly(P<0.05).The results of the CCK-8(cell counting kit-8,CCK-8)kit showed the optimal concentration of AS-IV 15 μg/mL and Ta-IIA 25 μg/mL.In vitro,CC3 expression was increased in the OGD group compared to the control group and decreased in the treated group compared to the OGD group.Conclusion AS-IV combined with Ta-IIA can not only reduce oxidative stress and inflammation in ischemic stroke rats,but also inhibit neuronal apoptosis by activating Nrf2/HO-1 pathway.