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Effects Of Tanshinone ?A On The PTEN-PI3K/AKT/mTOR Signaling Pathway After Cerebral Ischemia In Rats

Posted on:2021-02-09Degree:MasterType:Thesis
Country:ChinaCandidate:X XuFull Text:PDF
GTID:2404330611458439Subject:Neurology
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?Background? Tanshinone ?A is a drug extracted from the root of the plant salvia miltiorrhiza,and is commonly used clinically to treat cardiovascular and cerebrovascular diseases due to its effects of improving circulation,dilating blood vessels and repairing vascular endothelial injury.Further studies of tanshinone ?A have shown that tanshinone ?A is involved in regulating levels of nerve cells.Autophagy,also known as the normal death of the cell itself.In normal physiological conditions,the level of autophagy is relatively weak,mainly used to devour the aging organelles and some proteins and other substances.However,when the body is stimulated by abnormal physiological or pathological stimuli,the level of autophagy regulated by cells will increase,which will damage the organelles and have a significant impact on the normal structure of cells.In serious cases,normal cells of the body will die.For this reason,it also provides a target for drug research of treatment.At present,it has been found in literature that after cerebral ischemia,abnormal activity of autophagy in cells leads to death of normal tissues.It is well known that PI3K/Akt/mTOR pathway plays an important regulatory role in cell proliferation,growth,differentiation and survival,and tanshinone ?A plays an important regulatory role.In the ongoing research on autophagy signaling pathway,it has been found that PTEN,as a tumor suppressor gene,plays an important role in regulating the activation of PI3 K in the autophagy process,but there are no relevantstudies to reflect the autophagy expression of pten-pi3 k /AKT/mTOR after cerebral ischemia.Therefore,by verifying the regulating effect of PTEN on autophagy signal after cerebral ischemia,we can further understand the in-depth influence of tanshinone ?A on autophagy signal pathway.?Objective? To investigate the effect of tanshinone ?A on autophagy signaling pathway pten-pi3 k /AKT/mTOR in rats after cerebral ischemia.?Methods? According to the needs,80 healthy male rats with a body weight of250-280 g were randomly divided into two groups,namely,80 rats in the surgical group(MCAO)and 10 rats in the non-surgical group,and the rats in the surgical group were randomly and evenly divided into two groups.All rats were fed for 4 days according to the feeding conditions.One of the two groups in the operation group was fed tanshinone ?A during the feeding period,which was labeled as MCAO+TSA group,while the other group in the operation group was given normal saline,namely MCAO+NS group.The sham operation group had the same feeding conditions as the MCAO+NS group.The SD rats in the operation group were given the MCAO model,and their brains were extracted on day 1,3 and 7 according to the requirements.During the construction of the model,the rats in the operation group were observed and beaten by Zea Longa scoring criteria.Requirements for inclusion: 2-3 points.The expression of PTEN and respective phagocytes was detected in the immune formation.Western Blot can be to find out the expression levels of PI3 K,PTEN,PI3 K,AKT and mTOR.?Results? 1.The behavioral score showed that: in the surgery group,the MCAO+TSA group had a lower score than the MCAO+NS group,indicating that the occurrence of cerebral infarction in the rats in the tanshinone ?A group was less severe than that in the rats in the normal saline group,which again verified that tanshinone ?A had a definite effect on the treatment of cerebral infarction.2.Immunohistochemical microscopic observation of different proteins showed:(1)compared with the MCAO+NS group,the expression of PTEN protein in the non-surgical group was higher than that in the MCAO+NS group,while the expression levels of PI3 K,AKT and mTOR autophagy protein in the MCAO+NS group were significantly higher,with statistically significant differences.(2)compared with the sham group,the protein level of the rats in the operation group was significantly lower than that in the non-operation group.The expressions of AKT ?mTOR and PI3 K in the operation group were obvious raised compared with those in the non-operation group.(3)in the operation part,the expression of protein PTEN in MCAO+TSA group was higher than that in MCAO+NS group.The expressions of PI3 K,AKT and mTOR in MCAO+TSA group were smaller than those in MCAO+NS group,and the differences were statistically significant.3.Protein expression by WB method was found as follows:(1)compared with the MCAO+NS group,the non-operation group showed a higher expression level of protein PTEN,while the expression level of autophagy proteins PI3 K,AKT and mTOR was lower in the sham operation group,with big-time differences.(2)comparison between the operation group and the sham group: the expression of PTEN in the experiental group was significantly added;But protein PI3 K,AKT,mTOR expression level is high.(3)in the experiental form,the expressed standard of PTEN in the MCAO+TSA group increased compared with that in the MCAO+NS group.The expression levels of PI3 K,mTOR and AKT,those were lower in MCAO+TSA group than in MCAO+NS group,and the differences were very momentous.?Conclusion?1.After cerebral infarction,the expression of pten-pi3 k /AKT/mTOR increased;2.Tanshinone ?A can enhance the expression of PTEN in rats with cerebral infarction and reduce the expression level of the autophagy signaling pathway PI3K/AKT/mTOR,thereby reducing the inflammation in brain tissue of rats and protecting the brain of rats.
Keywords/Search Tags:Cerebral infarction, Tanshinone ?A, PTEN, PI3K
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