| Purposes:Cardiovascular disease?CVD?risk factors are commonly exposed in China.Timely reperfusion therapy to restore blood supply to ischemic myocardium is considered to be the most effective treatment to prevent myocardial necrosis,but reperfusion therapy itself may lead to an increase in myocardial damage.That is how myocardial ischemia reperfusion injury?MIRI?could occur.MIRI now is seriously threatening the lives of patients.There is a large count of literature showing that the occurrence of MIRI may be closely related to factors such as energy metabolism disorder,oxidative stress,Ca2+overload,inflammatory response,mitochondrial dysfunction and apoptosis.TMTXN is researched by Pro.ZhengJin.He combined the theory of Yi Nationality Medicine and the treatment theory of‘heartache,dizziness'from Yi Nationality.Previous studies have proved that TMTXN can cleared ROS to reduce their level.The clearance of ROS may be based on the Nrf2/ARE pathway.The Nrf2/ARE pathway also regulates the anti-apoptotic mechanism.Therefore,we infer that TMTXN can reduce MIRI through anti-oxidation and anti-apoptotic mechanisms by Nrf2/ARE pathway.The first part aims to study the unique theoretical basis of Yi Nationality Medicine and the principle and foundation of heartache caused by‘poisonous pathogen'.It explains the occurrence and development of heartache and the principles and methods of treatment,which provide new ideas for the prevention and treatment of heart pain-related diseases on the other hand.It is worth further mining its scientific core.The second to the fourth part of the purposes are to clarify the protective effect of TMTXN from Yi Nationality Medicine on MIRI rats based on Nrf2/ARE pathway by regulating mRNA and protein levels of Nrf2,SOD1,Bax,Bcl-2.Then discuss its mechanism perliminarily.In summary,the purposes of this study were to determine whether the anti-ischemic reperfusion injury was induced by anti-oxidation and anti-apoptotic necrosis based on the Nrf2/ARE pathway.Methods:1.56 SD male rats were randomly divided into 7 groups,namely control group,sham group,model group,TMTXN low dose group,TMTXN middle dose group,TMTXN high dose group,edaravone group.Rats in high,middle and low dose groups of TMTXN were given prophylactic administration.Rats in sham group were only threaded at the location of cardiac ligation.Except for the control group and the model group,the rats were ligated with the left anterior descending coronary artery for 30 min.Rats in edaravone group were injected with the femoral vein when they were ligated of 29 minutes.All rats were reperfused for 2h,and the classic MIRI rat model was replicated;2.Record the S-T segment deviation of the standard II lead ECG at each time point 10 min before ligation,ligation for 30 min,and reperfusion for 2h;3.The level of superoxide dismutase?SOD?in myocardial tissue was detected by xanthine oxidase method.4.The mRNA expression levels of Nrf2,SOD1,Bax and Bcl-2 in myocardial tissue were detected by RT-qPCR method.5.The protein expression levels of Nrf2,SOD1,Bax and Bcl-2 in myocardial tissue were detected by Western Blot method.Results:1.Yi Nationality Medicine has unique theoretical basis and the principle and foundation of heartache caused by‘poisonous pathogen'.It explains the occurrence and development of heartache and the principles and methods of treatment,which provide new ideas for the prevention and treatment of heart pain-related diseases on the other hand.It is worth further mining its scientific core.2.Compared with sham group,the S-T segment deviation of the model group was larger,the difference was statistically significant?P<0.05?,the SOD was obvious incresed in myocardial tissue,the difference was statistically significant?P<0.0001?;3.Compared with model group,all TMTXN dose groups had inhibitory effect on S-T segment deviation in MIRI rats,the difference was statistically significant?P<0.05?,all TMTXN dose groups can increase the SOD activity in the myocardial tissue?P<0.05,P<0.01,P<0.001?.4.Compared with blank control group,the mRNA expression levels of Nrf2 and SOD1 in the model group were statistically significant?P<0.05,P<0.01?,all TMTXN dose groups and edaravone group were statistically significant from the model group,and their expression levels were higher than those of the model group.The difference was statistically significant?P<0.05,P<0.01,P<0.001,P<0.0001?.Which indicate that Nrf2 and SOD1 gene which associated with Nrf2/ARE pathway show the effect of alleviating MIRI by antioxidnat.5.Compared with blank control group,the mRNA expression levels of Bax and Bcl-2 in model group were statistically significant?P<0.0001?.All TMTXN dose groups were statistically different from model group.The mRNA expression of Bax was lower than that of model group and the expression of Bcl-2 was higher than that of model group.The difference was statistically significant?P<0.05,P<0.01,P<0.0001?.The ratio of Bax/Bcl-2 was much lower than that of model group,and the difference was statistically significant?P<0.0001?.Which indicated that the Bax and Bcl-2 genes associated with the Nrf2/ARE pathway showed TMTXN could be anti-apoptosis to reduce the effects of MIRI.6.Compared with blank control group,the protein expression levels of Nrf2 and SOD1 in model group were statistically significant?P<0.01,P<0.001?.The TMTXN high dose group and daravone group were significantly difference than that in model group,the difference was statistically significant?P<0.05?.All TMTXN dose groups showed a certain dose-effect relationship,which indicated that Nrf2 and SOD1proteins expression levels which are related to the Nrf2/ARE pathway shown that TMTXN has antioxidant effects to alleviate MIRI.7.Compared with blank control group,the protein expression levels of Bax and Bcl-2 in model group were statistically significant?P<0.01,P<0.0001?,TMTXN high and middle dose groups and edaravone group were significantly different from model group.The protein expression level of Bax was lower than that of model group and the expression level of Bcl-2 was higher than that of model group.The difference was statistically significant?P<0.05,P<0.01,P<0.0001?.All TMTXN dose groups showed a certain dose-effect relationship.The ratio of Bax/Bcl-2 in all TMTXN dose groups and edaravone group was lower than that of model group.The difference was statistically significant?P<0.05,P<0.01,P<0.0001?.Which indicated that the protein expression of Bax and Bcl-2 in the Nrf2/ARE pathway was associated with the anti-apoptosis of MIRI by TMTXN.Conclusion:1.Yi Nationality Medicine has its own unique theoretical foundation and the principle and foundation of‘heart pathogen',which deserves to further explore its scientific core.2.TMTXN can effectively alleviate MIRI on rat.3.TMTXN can relieve MIRI by regulating Nrf2,SOD1,Bax and Bcl-2 on Nrf2/ARE pathway for antioxidant and anti-apoptotic. |
PDF Full Text Request