Study On Therapeutic Effect And Mechanism Of FT Injection On Ischemic Stroke

Stroke poses a threat to national health due to its characteristics of high age-related morbidity,high regional morbidity,high prognosis recurrence rate and high fatality rate.Although people have never stopped the research on stroke,no cure has been found so far.Ginkgo biloba and Chuanxiong alone can repair damage to stroke.Ginkgo biloba PE,ginkgolide,and LP are the key ingredients.Folium Ginkgo Extract and Tertram Ethypyrazine sodium chloride injection（FT injection）,which is made by combined application Clinical application in the treatment of stroke is effective,but how FT injection works in the non-acute phase of stroke has not yet been reported.The relevant molecular mechanism has not yet been elucidated.In this paper,FT injection will be used as the research object to establish a rat model of middle cerebral artery ischemia/reperfusion injury（MCAO/R）,breaking through previous experimental studies,pre-administration failed to simulate ischemic cerebral apoplexy patients in the treatment of the midbrain injury recovery process,uses the abdominal cavity injection way to give longterm drug treatment model rats for 14 days.Combined with the efficacy indicators such as behavioral score,brain tissue infarction volume and pathological section staining,and through ELISA,immunofluorescence staining and Western Blot technology,the efficacy and effect of FT injection on cerebral ischemia/reperfusion injury in the non-acute phase were explored.The main research methods and results are as follows:（1）The SD rat model of middle cerebral artery ischemia/reperfusion injury was established by suture method,and the model rats were treated with drugs for 14 days by intraperitoneal injection,and the injury recovery degree of rats in each group was compared.By observing the flexibility of voluntary activities of rats,combined with the 5-level scoring method of neurological function,the degree of recovery of damaged rat cranial nerves after receiving drug treatment was distinguished.Using TTC staining method combined with the measurement results of multiple indicators of pathological section staining,it was analyzed whether FT injection had a repairing effect on the injured area of the rat brain.The results confirmed that FT injection did have the pharmacodynamic effect against cerebral ischemia/reperfusion injury.The therapeutic effect of FT injection with a dosage of 12.5 ml/kg was not significant,and the efficacy of 25 ml/kg and 50 ml/kg was significant.The infarct volume was smaller;the cell arrangement in the lesion area recovered neatly and tightly,and the number of apoptosis decreased.It is suggested that FT injection has a repairing effect on cerebral ischemia/reperfusion injury.（2）The mechanism of FT injection in repairing ischemia/reperfusion injury was explored by ELISA detection method combined with Western Blot detection method.The expression of oxidative stress-related factors 4-HNE,8-OHdG,NOX,and PC decreased after FT injection was administered for 14 days,and the mechanism of action may be related to Akt/Nrf2/HO-1.Immunofluorescence staining was used to observe the changes of astrocyte marker GFAP and combined with ELISA to detect the expression of inflammation-related factors.The results showed that FT injection could inhibit abnormal proliferation of astrocytes,inhibit serum and the expression levels of inflammatory factors CD11α,ICAM-1,IL-1β,IL-6,KYN,MCP-1,TNF-α,and caspase-1 increased in the lesion tissue,and the mechanism may be related to NLRP3/IL-1β correlation.FT injection can promote the expression of bFGF2,PDGF and TGF-β in serum.Inhibition of MMP-3 and MMP-9 expression and angiogenesis may be related to the activation of SIRT1-PGC-1α/VEGF signaling pathway.In conclusion,the pharmacodynamic effect of FT injection in repairing ischemic stroke injury may be reflected in repairing nerve function and reducing the volume of cerebral infarction.The mechanism of antioxidant stress may be related to the activation of Akt/Nrf2/HO-1 signaling pathway.Inhibition of NLRP3/IL-1β pathway may be involved in the mechanism of anti-inflammatory response.The mechanisms promoting angiogenesis are associated with the activation of SIRT1-PGC-1α/VEGF signaling pathway.