Experimental Study On Myocardial Protective Effects Of Caspases Inhibitor For Ischemia-reperfusion Injury

Objective: To observe the protective effect of caspase inhibitor z-vad-fmk when adding into St.ThomasII cardioplegia and storage solution, and explore its possible mechanisms and rational therapeutic pathway. Study its influence on Bcl-2/Bax protein expression and further explore its molecular mechanism, thereby providing rational fundation for clinical application.Methods: 42 new Zealand rabbits were randomly assigned to three groups. Normal group: The hearts were perfused without cardioplegia and heart storage. Control group: The hearts were arrested with St.ThomasII cardioplegia and stored in the same solution (n=18). Experimental group: the hearts were arrested with St.ThomasII plus z-vad-fmk solution and stored in the same solution (n=18). All rabbit hearts were stored for 4h,8h and 16h with 4℃hypothermia, and underwent 60 minutes of reperfusion (37℃). On the Langendorff perfusion apparatus, the parameters of hemodynamics (HR,CF,LVDP,LVEDP,±dp/dtmax,SV) and cardiac function (RPP) , the incidence of arrhythmias, the myocardial enzymes (LDH,CK,CK-MB) were measured before and during reperfusion. Apoptotic myocytes were detected with transmission electron microscope and terminal deoxynucleotide transferase-mediated deoxyuridine-biofin nick end labeling (TUNEL) method. The expression of Bcl-2 and Bax protein were detected by Immunohistochemistry analysis. Meanwhile, myocardial water content and ultra structure were also examined.Results:(1) After the heart were stored for 4h, 6h, 8h, the recovery of hemodynamics and cardiac function of the experimental group were significantly better than in the control group during reperfusion (P<0.05), the myocardial enzymes leakage and water content was significantly decreased (P<0.05) and the damage of myocardial ultra structure was little in...