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Hydrogen Through PI3K/Akt Signaling Pathway Inhibit Cell Apoptosis Of Myocardial Ischemia-reperfusion Injury In Diabetic Rats

Posted on:2015-08-29Degree:MasterType:Thesis
Country:ChinaCandidate:R WeiFull Text:PDF
GTID:2284330431496546Subject:Surgery
Abstract/Summary:PDF Full Text Request
In recent years,with the development of interventional fibrinolytic therapyand percutane-ous transluminal coronary recanali-gation in minimally invasivesurgery, the prevention of early postoperative complications has becoming a hotspot of current research, and one of the most common and most seriouscomplications is myocardial ischemia-reperfusion (I/R) injury,and it gainedthe people more and more attention.Diabetic mellitus is a clinical commonchronic disease, the epidemiological and clinical studies showed that theincidence of ischemic heart disease in diabetic crowd is much higher thanpeople without diabetes, and compared with normal people, theischemia-reperfusion injury is more serious.At present, people will set his sightson diabetic mellitus which get more influence on myocardialischemia-reperfusion injury.In recent years a large number of studies haveshown that, the hydrogen is a kind of important physiological regulatory factor,on cell and organ level, with a clear selectivity of anti-oxidation,anti-inflammatory and anti apoptosis viscera protection, such as copyingdiabetic rats model, this study observed by intraperitoneal injection of hydrogenon diabetic rats to inhibit myocardial ischemia reperfusion injury of myocardialcell apoptosis and apoptosis related proteins expression, to provide theoreticalfoundation the effect of perioperative treatment for diabetes patients.Part I Effect of Hydrogen on ischemia/reperfusion-induced cardiocyte apoptosisin diabetic ratsObjective: To study the effect of Hydrogen on ischemia/reperfusion (I/R)-induced cardiocyte apoptosis and apoptosis related proteins expression indiabetic rats. Methods:Diabetes mellitus was induced by intraperitoneal injection ofstreptozotocin(STZ),then feed4weeks before build ischemia/reperfusionmodel.60SD male rats,weight during300-350g,were randomly divided to sixgroups: non-diabetic sham-operated group(NS),non-diabetic I/R group(NI/R),non-diabetic hydrogen treated group(NH),diabetic sham-operatedgroup(DS),diabetic I/R group(DI/R)and diabetic hydrogen treatedgroup(DH),each group has10rats.The cardiac muscle I/R model was made by30min occlusion of the left anterior descending coronary artery and2hreperfusion.The rats in Hydrogen group were treated with5ml/kg hydrogen byintraperitoneal administration at the beginning of reperfusion.The apoptosisindex(AI) was calculated by TUNEL.The positive expressions of Bcl-2, Bax incardiomyocytes were respectively detected by immunohistochemistry.Results:The apoptotic rates of cardiomyocytes and the positive expressions ofBcl-2, Bax were significantly increased (P<0.01), Compared with I/R group, thepositive expressions of Bcl-2were increased(P<0.01),at the same time,thepositive expressions of Bax was decreased(P<0.01).Conclusion: Hydrogen inject by intraperitoneal method on myocardialischemia-reperfusion injury of diabetic rats has a protective effect;Itsmechanism may be related to its inhibiting myocardial apoptosis by advancedthe Bcl-2protein expression and reduced the Bax protein expression.Part II The role of PI3K/Akt signaling pathway in Hydrogen inhibits myocardialischemia/reperfusion-induced cardiocyte apoptosis in diabetic ratsObjective: To study the connection between PI3K/Akt signaling pathwayand Hydrogen inhibits myocardial ischemia/reperfusion (I/R)-inducedcardiocyte apoptosis in diabetic rats.Methods:Diabetes mellitus was induced by intraperitoneal injection ofstreptozotocin(STZ),then feed4weeks before build ischemia/reperfusionmodel.40SD male diabetic rats,weight during300-350g,were randomly dividedto four groups: diabetic sham-operated group(DS),diabetic I/R group(DI/R)anddiabetic hydrogen treated group(DH),diabetic hydrogen treated group withLY294002(DH+LY294002),each group has10rats.The cardiac muscle I/Rmodel was made by30min occlusion of the left anterior descending coronaryartery and2h reperfusion.The rats in Hydrogen group were treated with5ml/kghydrogen by intraperitoneal administration at the beginning of reperfusion.Thepositive expressions of Bad in cardiomyocytes were respectively detected byimmunohistochemistry.And the expressions of pAkt mRNA in diabetic groups were detected by RT-PCR.Results:Compared with DS group,the expresssions of Bad wereincreased(P<0.01) in DI/R group,DH group and DH+LY294002group;Compared with DI/R group,the expresssions of Bad weredecreased(P<0.01) in DH group,and have no significant difference inDH+LY294002group(P>0.05);Compared with DH group,the expresssions ofBad were increased(P<0.01) in DH+LY294002group.Compared with DSgroup,the expresssions of pAkt mRNA were increased(P<0.01) in DI/Rgroup,DH group and DH+LY294002group;Compared with DI/R group,theexpresssions of pAkt mRNA were increased(P<0.01) in DH group,and have nosignificant difference in DH+LY294002group(P>0.05);Compared with DHgroup,the expresssions of Bad were decreased(P<0.01) in DH+LY294002group.Conclusion:Activating PI3K/Akt signaling pathway may play a part inHydrogen inhibits myocardial ischemia/reperfusion-induced cardiocyteapoptosis in diabetic rats.
Keywords/Search Tags:hydrogen, diabetes, myocardium, ischemia-reperfusion, PI3K/Akt signaling pathway
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