| Ischemic stroke is mostly due to atherosclerosis,vasculitis,which causes embolization of large arteries or their branches.And in the pathological process of cardiovascular diseases such as atrial fibrillation,the shed emboli entered the blood,which caused the blood vessels in the brain to be blocked,and the blood could not supply the brain tissue in time.The damage mechanism of ischemic stroke is very complicated,and cerebral ischemia-reperfusion injury is one of the important causes of serious irreversible damage to brain tissue.Studies have shown that endoplasmic reticulum stress(ERS)is closely related to apoptosis caused by ischemia and hypoxia.Safflower injection is a sterile aqueous solution extracted from single safflower by boiling and alcohol precipitation.It has the effect of promoting blood circulation and removing blood stasis,and is widely used in the treatment of heart,cerebrovascular diseases and gynecological diseases.A large number of studies have shown that safflower injection can inhibit brain cell apoptosis and have a protective effect on brain cells.However,the protective effect of safflower injection on cerebral ischemia-reperfusion injury and its mechanism need to be further studied.Objective: To explore the mechanism of safflower injection in the treatment of ischemic stroke based on endoplasmic reticulum stress and anti-apoptotic pathway.Methods: 24 SD rats were randomly divided into 4 groups: A: sham operation group,B: model group,C: edaravone group,D: safflower injection group.Use modified suture method to make rat middle artery occlusion model.Tail vein injection is used as the method of administration.Modified Zea Longa score was performed on the brain tissue of experimental animals 24 hours after administration.Blood is taken from the abdominal aorta and the serum is separated.The brain tissue is preserved in tissue preservation solution and paraformaldehyde,and the following index batches are tested: 1.The TTC staining method was used to measure the cerebral infarct volume of experimental animals.2.ELISA method was used to detect the level of hypersensitive C-reactive protein in the serum of experimental rats in each group.3.The TUNEL method was used to detect the apoptosis of hippocampus in each group of experimental rats.4.Immunohistochemical method was used to detect the expression of CHOP,GRP78,Caspase-3 and Bcl-2 in the brain tissue of each group of experimental rats,and the mechanism of safflower injection in the treatment of ischemic stroke was studied from the ERS approach.5.Using RT-qPCR to study the effect of safflower injection on the mRNA expression of GRP78,CHOP,PERK,ATF6,IRE1 in the brain tissue of model rats.Results: 1.The improved Zea Longa scoring results showed that,compared with the model group,the scores of edaravone group and the safflower injection group were significantly lower,with statistical significance(p<0.05);There was no significant difference in scores between the edaravone group and the safflower injection group.The results of TTC staining showed that the cerebral infarction volume of rats in the treatment group was significantly lower than that in the model group(p <0.05).2.Compared with the model group,the hypersensitive C-reactive inflammatory biomarkers in the serum of rats in the edaravone group and the safflower injection group were significantly lower,with statistical significance(p<0.05);Compared with edaravone group,the safflower injection group was not statistically significant.It shows that both safflower injection and edaravone can reduce the inflammatory response of ischemic stroke.3.The TUNEL method showed that the brain cell apoptosis rate of the drug group was lower than that of the model group,which was statistically significant(p <0.05).4.The expression of GRP78 in the safflower injection and edaravone groups was up-regulated,while the expression of CHOP was down-regulated,which was statistically significant compared with the model group(p <0.05);Compared with the model group,the expression of Caspase-3 was down-regulated in the safflower injection and edaravone group,which was statistically significant(p <0.05),and the expression of Bcl-2 was up-regulated,which was statistically significant(p <0.05).5.RT-qPCR results showed that when the rats developed ischemic stroke,the expression of GRP78 mRNA in the safflower injection group and edaravone group was higher than that of the model group,and the expression of CHOP mRNA was lower than that of the model group.Compared with the model group,the expression of PERK mRNA in the safflower injection group and edaravone group was lower than that in the model group,which was statistically significant(p <0.05).Conclusion: Safflower injection can reduce the infarct volume of reperfusion model rats,reduce the apoptosis of brain cells in ischemia-reperfusion model rats,reduce local inflammation,inhibit the expression of CHOP,Caspase-3,PERK,and promote GRP78,Bcl-2 expression.Blocking the response through the PERK pathway may be one of the mechanisms of safflower injection in the treatment of ischemic stroke. |
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