| Objective: To investigate whether IM-12 exerts its effects on attenu ating rt-PA-induced hemorrhagic transformation after rat acute ischemic stroke by regulating changes in the Wnt/?-catenin signaling pathway.Methods: 24 rats were randomly divided into four groups as follows: Sham group—rats underwent the same surgical procedure,but the filament was not inserted and they received 1 mL of dimethyl sulfoxide(1 % DMSO in saline);Vehicle group—rats underwent MCAO and received 1 mL of DMSO;rt-PA group—rats underwent MCAO and received rt-PA(10 mg/kg)at 4 h after MCAO;and rt-PA+IM-12 group—rats underwent MCAO and received intraperitoneal IM-12(25 mg/kg,dissolved in 1 mL 1 % DMSO)immediately after rt-PA injection at 4 h after MCAO.After treatment,morphological detection was performed for each group of rats,as follows: TTC staining was used to detect the volume of cerebral infarction;EBI was used to evaluate the BBB 24 hours after reperfusion.The content of hemoglobin was determined by spectrophotometry to evaluate cerebral hemorrhage.Changes of GSK-3?,?-catenin and AKT were detected by Western Blot after 24 hours of reperfusion.Results:(1)Changes in Cerebral Infarction: Infarct volume in the rt-PA group was significantly greater than that of the vehicle-treated MCAO group(P<0.05).Administration of IM-12 reduced the infarct volume compared with that in the rt-PA group(P<0.05),while increased in the Vehicle group(P<0.05).No infarct area was detected in the sham group.(2)Changes in Blood–Brain Barrier Permeability: Our results showed that EBI in the rt-PA group was significantly greater than that in the vehicle group(P<0.05)but was reduced by IM-12 treatment(P<0.05).(3)Changes in rt-PA-Induced Hemorrhage in Ischemic Brain Tissue: Hemoglobin content index was significantly higher in the rt-PA group than in the vehicle group(P<0.05)but was significantly reduced by IM-12 treatment(P<0.05).(4)Western Blot detection: Western blot analysis showed that the expression of phosphorylated AKT was significantly higher in the rt-PA and rt-PA+IM-12 group than in the vehicle group(P<0.01).However,the expression of phosphorylated GSK-3? was significantly lower in the rt-PA+IM-12 group than in the rt-PA group(P<0.01).Conclusions:(1))IM-12 can reduce the volume of cerebral infarction in ischemic stroke rats treated with rt-PA and maintain the stability of the blood-brain-barrier;(2)IM-12 can reduce the risk of cerebral hemorrhage transformation after rt-PA treatment in ischemic stroke rats;(3)IM-12 regulate the Wnt/?-catenin signal pathway to reduce the risk of cerebral hemorrhage transformation after rt-PA treatment in ischemic stroke rats which is related with the function of BBB. |
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