Study On The Protective Effect And Correlation Of Bundle Therapy On Myocardial Infarction In Rats

Background In recent years,the field of stem cells has developed rapidly,and the transplantation of mesenchymal stem cells(MSCs)has broad prospects for the treatment of myocardial infarction(MI).However,the heart homing rate and survival rate of MSC transplantation are low.Previous studies have shown that atorvastatin can effectively improve the microenvironment around MI and increase the survival rate of bone mesenchymal stem cells(BMSC).However,a large number of BMSC are trapped in pulmonary blood vessels during transplantation.Previous researches suggested that Treprostinil can effectively expand the pulmonary blood vessels.Therefore,we speculate that the addition of Treprostinil can further improve the efficacy of BMSC.Methods In vitro experiment: we isolate and culture BMSC to the third generation,and perform flow cytometry to identify BMSC.In vivo experiment: the heart-squeezing-coronary artery ligation method was used to establish a rat model of MI and randomly divided into: Treprostinil and atorvastatin combined with BMSC group,atorvastatin and saline combined with BMSC group,Treprostinil and saline combined with BMSC group and saline combined with BMSC group.Atorvastatin and Treprostinil were administered for 1 week and then BMSC transplantation was performed.One week after MI,the cardiac function of the rats was detected by echocardiography,inflammatory cell infiltration and angiogenesis in the peripheral area of MI were detected by histopathology,and the expression levels of SDF-1,e NOS and inflammatory factors in the cardiac tissue of the peripheral area of myocardial infarction were detected by Western-Blot.At 4 weeks,the degree of myocardial fibrosis was detected by MASSON staining and the rat heart function was measured again.Results Compared with the normal saline group,atorvastatin gavage for 1 week can significantly increase the expression of SDF-1α and e NOS in the myocardial tissue around the infarct area,significantly down-regulate the expression of TNF-α and CRP protein to inhibit inflammation and promote angiogenesis.Treprostinil can also significantly reduce the expression of CRP protein.Compared with Treprostinil or saline combined with BMSC group,atorvastatin combined with BMSC can significantly reduce MI and improve cardiac function,which is mainly manifested by the increase in left ventricular ejection fraction(LVEF)and left ventricular short axis shortening rate(LVFS).Treprostinil and atorvastatin combined with BMSC further improved the heart function of rats with myocardial infarction,showing that the change of LVEF and LVFS improved more.Conclusion Atorvastatin can improve the microenvironment around MI by inhibiting inflammation and promoting angiogenesis.Treprostinil and atorvastatin combined with BMSC can effectively reduce myocardial fibrosis and improve myocardium function in infarcted rats to supplement the evidence and provides new ideas for the cell therapy of myocardial infarction.