The Change Of P38/JNK MAPK Pathway And Its Influence On Myocardial Reperfusion Injury In Classical And Improved Algorithm Of Postconditioning In Rat

Part One:The Change of Phospho-p38/JNK and Its Influence on Myocardial Reperfusion Injury in Mechanical PostconditioningObjective:Study the change of Phospho-p38/JNK MAPK and its influence on myocardial reperfusion injury in mechanical postconditioning. Methods:70 rats were randomly divided into 7 groups:sham, reperfusion/injury(R/I), postconditioning (Post), SP600125 (SP), SB203580 (SB), Anisomycin+Post (Ani+Post) and Anisomycin (Ani). Results:Compared with R/I group, the level of serum marker, apoptotic index, infarct size, the expression of molecules leading to apoptosis in SP and SB group were all significantly lower (P< 0.05). The expression of P-JNK in SP group was lower than R/I group (P<0.05) and similar with Post group (P>0.05). The expression of P-p38 in SB group was lower than R/I group (P<0.05) and similar with Post group (P>0.05). On the other hand Ani+Post group lost cardioprotection partly, all variables in Ani group were similar with those in R/I group (P>0.05). Conclusion:Postconditioning could inhibit phosphorylation of p38/JNK MAPK, through which it attenuates cardiomyocyte apoptosis by both death receptor and mitochondria pathway.Part Two:Improved Algorithm-Gradual Increased Reperfusion in Postconditioning Plays Better Role in CardioprotectionObjective:Study cardioprotection of different postconditioning algorithm, and investigate the mechanism in the process. Methods:60 rats were randomly divided into 5 groups:sham, reperfusion/injury(R/I), postconditioning (Post), gradual decreased reperfusion (GDR), equal reperfusion(ER), and gradual increased reperfusion (GIR). Results:Compared with R/I group, the level of homodynamic variables, serum marker of myocardium, apoptotic index, infarct size, the expression molecules leading to apoptosis in GDR, ER and GIR group were lower significantly (P<0.05). The difference of GIR was the most, and then was ER and the last was GDR group. Compared with ER group, except for infarct size was similar (P>0.05), variables in GDR group were all much better (P <0.05). Conclusion:Gradual increased reperfusion algorithm of postconditioning could relieve reperfusion injury more significantly, this is probably because it could activate ERK and inhibit p38/JNK MAPK more seriously.Part Three:Pharmacological Postconditioning with Lactic Acid and Low Dose of Edaravone could Attenuate Myocardial Reperfusion InjuryObjective:The aim of this study was to test the hypothesis that pharmacological postconditioning with lactic acid and low dose of edaravone could mimic the upper trigger of mechanical postconditioning and relieve reperfusion injury. Methods:108 rats were randomly divided into 6 groups:sham, reperfusion/injury(R/I), postconditioning (Post), lactic acid (Lac), low dose of edaravone (Eda), and lactic acid+low dose of edaravone edaravone (Lac+Eda).Results:Compared with Post group, pH of blood from right atrium in Lac and Lac+Eda group were similar (P>0.05); and the level of MDA and SOD in Eda and Lac+Eda group were also similar (P>0.05). The level of homodynamic variables, serum marker of myocardium, apoptotic index, infarct size, the expression molecules leading to apoptosis in Lac+Eda group were all similar with Post group(P>0.05). Lac and Eda group could mimic the cardioprotection partly.Conclusion:Lactic acid injected in ischemic myocardium at the onset of reperfusion could mimic the prolonged local acidosis in postconditioning, and pharmacological postconditioning with lactic acid and low dose of edaravone could mimic the upper trigger of mechanical postconditioning and attenuate myocardial reperfusion injury.