The Research Of Everolimus Anti-cardial Fibrosis By Upregulating TET1 Protein

Background:Myocardial infarction(MI)have been one of most threatening desesae for human health.It plays a important role in human life force and life quality.Myocardial fibrosis is a important pathological character after MI.At present,there are few effective cures for MI.And the cure for MI now can only relief symptom.But can not relief or changover developement of Myocardial fibrosis.So study the mitigation methods of myocardial fibrosis have great clinical significance.Everolimus is a drag that can anti-tumor and anti-proliferation of vascular.It play a impotant role in a variety of biological processes.Some research show that everolimus have the ability to resistant proliferation of fibroblast.On the other hand,if everolimus have the ability of anti-myocardial fibrosis is not clear now.TET protein is a kind of demethylase that can convert 5-mc to 5-hmc,regulate the DNA methylation level and then promote gene expression.Previous studies have shown that TET proteins play a important role in maintaining pluripotency of embroynic and generation and development of tumor.Recent research show that TET protein also parcipated in anti-myocardial fibrosis,so that can relief development of organs fibrosis.Objective:We make MI model in C57BL/6 mouse,and intervene them with everolimus.Observe pathologic change of infarct myocarduim.Detect m RNA exprssion of TET protein in myocardium after MI.We find that m RNA exprssion increase while the time of MI increase.So we make a further testify by Western blotting.So that preliminary discussion effect of everolimus in process of myocardial fibrosis.And whether everolimus play a part in anti-cardial infarction by activiting TET1 protein.Method:After MI there are 24 C57BL/6 mice servive.Divide into three groups respectly:MI group and MI+everolimuse group and Normal group.The treated group gavage with everolimus 3mg/kg/d.Get cardium and keep it in liqued netrogen or treat it by PFA4%.Observe poliferation of myocardium collagen by HE staining and Masson staining..Detect m RNA expression of TET1?TET2?TET3 and Col?/Col? in infarction region of mouse.And western blot to test TET1 protein expression.Results:1.HE and Masson staining show that there is obvious proliferation of fibroblast in infarct edge region of mouse.While the degree of myocardial fibrosis is relieved when compared with treatment group.2.TET1 is up regulation by everolimus,and everolimus make on difference on TET2 and TET3.B Western blot is in line with m RNA results.Conclusion: From our experimental finding,we can make a conclusion that everolimus have the ability of anti-cardial fibrosis.And evrolimus may anti-cardial fibrosis by upregulating TET1 protein.