| Cerebral ischemia is a common disease with high mortality and morbidity,which brings a heavy burden to the society and the family.In recent years,with the acceleration of social aging process and the change of people's lifestyle,the incidence of ischemic cerebrovascular disease is increasing year by year.At present,intravenous thrombolytic therapy is mainly used in the treatment of ischemic cerebrovascular disease,but the strict 3 h time window is the main obstacle of acute venous thrombolysis.Therefore,to explore the new therapeutic targets has become a major task and challenge in this field.The traditional Chinese medicine astragalus,a legume herb,has the effect of tonifying Qi,detoxicating and invigorating blood circulation.At present,the application of astragalus combined with other drugs in the treatment of cerebrovascular disease is quite common,while the application of astragalus monomer is a new exploration.It has been found that astragaloside IV is one of the three most effective components of astragalus,which has a significant effect on the repair of nerve cells.Autophagy,which is widely used in eukaryotes,plays an important role in maintaining the homeostasis of the intracellular environment.It is undisputed that autophagy participates in cerebral ischemia,but there is no consensus effect of autophagy in the process.In this study,a rat model of focal cerebral ischemia-reperfusion injury was established by modified thread embolism method,to simulated the pathophysiological process of clinical ischemic cerebrovascular disease,observed the therapeutic effect and the role of autophagy in the disease by astragaloside IV.The First Part Effects of astragaloside IV on the focal cerebral ischemia reperfusion injury in ratsObjective:To investigate the effect of astragaloside IV on focal cerebral ischemia reperfusion injury in rats.Methods:The focal cerebral ischemia reperfusion of rat left middle cerebral artery occlusion(MCAO)was induced by suture method.Male SD rats were randomly divided into sham operation group,cerebral ischemia reperfusion group,astragaloside IV group and solvent control group.Except for the sham operation group,the others were subjected to ischemia 2 h and reperfusion 24 h.Then,rats with successful modeling were chosen for the detection of various indexes.Astragaloside IV group was injected intraperitoneally with astragaloside IV(20 mg·kg-1)at the same time as reperfusion,while solvent control group was injected with the same amount of solvent.TTC staining was used to detect the volume of cerebral infarction,and Nissl staining to observe the changes of histomorphology,and transmission electron microscope(TEM)to observe the ultrastructure of the cells.Results:There was no neurological deficit in the sham operation group,and the volume of cerebral infarction was zero.Compared with the sham operation group,there were some increased neurological deficits,nerve cell damage and cerebral infarction volume in other groups(P<0.05);Compared with the cerebral ischemia reperfusion group,the nerve function damage could be significantly improved,the damage of neurons reduced,and the volume of cerebral infarction decreased(P<0.05)in astragaloside IV group,and there was no obvious change in the solvent control group(P>0.05).Summary:Astragaloside IV can reduce the focal cerebral ischemia reperfusion injury in rats and protects nerve cells from damage.The Second Part Effects of astragaloside IV on autophagy in rats with cerebral ischemia reperfusion injuryObjective:To investigate the effects of astragaloside IV(AS-IV)on autophagy in rats with cerebral ischemia reperfusion injury.Methods:Male SD rats were randomly divided into sham operation group(Sham),ischemia reperfusion group(I/R),solvent control group(Solvent),AS-IV group,AS-IV+autophagy inhibitor group(AS-IV+3-MA),autophagy inhibitor group(3-MA)and autophagy activator group(Rapa).Except for the sham operation group,the others were subjected to ischemia 2 h and reperfusion 24 h.The rats with successful modeling were selected according to Zea Longa scoring criteria.The volume of cerebral infarction was measured by TTC staining method.The morphological changes of nerve cells in rats were observed with Nissl staining.The phenomenon of autophagy was observed under transmission electron microscope(TEM).The protein expression of Beclin1 and LC3-? was determined by Werstern blotting.Results:No neurological deficit in sham operation group was observed,and the cerebral infarction was not founed.Compared with Sham group,obvious cerebral infarction was observed,the Nissl bodies were small in size and number,stained light,typical autophagosomes were observed,and the protein expression of Beclin1 and LC3-? was increased in I/R group(P<0.05).Compared with I/R group,the volume of cerebral infarction decreased obviously,and neurological deficit restored significantly,the number of autophagosome was grew,the protein expression of Beclin1 and LC3-? was increased in AS-IV group and Rapa group(P<0.05);However,no significant difference between Solvent group and I/R group was observed(P>0.05).Compared with AS-IV group,the neurological deficit was serious,the volume of cerebral infarction and the number of autophagosome was grew,while the expression of Beclin1 and LC3-? was decreased in AS-IV+3-MA group and 3-MA group(P<0.05).Summary:Astragaloside IV may play an important role in attenuating cerebral ischemia reperfusion injury by activating autophagy.Conclusion:Astragaloside IV can reduce the focal cerebral ischemia reperfusion injury in rats and protects nerve cells from damage.It plays an important role in attenuating cerebral ischemia reperfusion injury by activating autophagy. |
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