| Objective PPARs function as regulators of lipid and lipoproteinmetabolism and glucose homeostasis and influence cellular proliferation,differentiation and apoptosis. The hypolipidemic Fenofibrate and theantidiabetic Rosiglitazone are synthetic ligands for PPAR alpha and PPARgamma, respectively. In addition,there are many studies to estimate PPARsplay a role in inflammation control ,but few experiments to study theeffects of Rosiglitazone and Fenofibrate on cardiomyocyte apoptosis inrats after ischemia/reperfusion injury.This study will first observe theeffects of Rosiglitazone and Fenofibrate on cardiomyocyte apoptosis andexpression of Bcl-2,Bax and NF-κB gene proteins after acute ischemiaand reperfusion in rats and elucidate the possible mechanisms. Methods Forty SD rats were randomly divided into four groups asfollows: (1) Sham-operation group (n=10); (2) Ischemia-reperfusion group(n=10):the left coronary artery was occluded for 30 min followed byreperfusion respectively for 6 hours; (3) Rosiglitazone group (n=10): ratswere received ischemia/reperfusion with pretreatment of 3mg/kg/dRosiglitazone by mouth for 7 days, and the last dose was given 1 hourbefore operation. (4) Fenofibrate group (n=10): rats were received I-Rwith pretreatment of 80mg/kg/d Fenofibrate by mouth for 7 days, and thelast dose was given 1 hour before operation.The blood sample andmyocardium was prepared to measure the activity of SOD andMDA,respectively.The TdT-mediated dUTP nick end labeling (TUNEL)method was used to detect apoptotic myocytes in different groups.Bax ,Bcl-2 and NF-κB gene proteins expression in myocardium wereanalyzed by immunohistochemical technique. Results The activity of MDA in myocardium increased and theactivity of SOD in serum decreased obviously in Ischemia-reperfusiongroup. The activity of SOD in Rosiglitazone and Fenofibrate group weresignificantly higher (72.664±10.313, 83.0717±8.977 respectively)thanthose in ischemia-reperfusion group(43.476±7.499)(P<0.05). Theactivity of MDA in Rosiglitazone and Fenofibrate group were significantlylower (4.7552±0.3369 , 4.2577±0.4992 respectively) than those inischemia-reperfusion group(7.3457±0.4225) (P<0.05). The apoptotic cardiomytocytes were not observed in theSham-operation group and were found in ischemia fields in theIschemia-reperfusion group. The number of apoptotic cardiomytocytes inIschemia-reperfusion group were significantly more (16.17±5.02), thanthose in Rosiglitazone and Fenofibrate group(8.61±2.07 , 9.14±2.46respectively) (P<0.01). The expression of NF-κB in myocardium inRosiglitazone and Fenofibrate group(10.10±3.84,9.24±3.12 respectively)was less than those of Ischemia-reperfusion group(18.60±7.21)(P<0.05).Further, the number of Bcl-2/ Bax positive cells index were significantlyhigher in Rosiglitazone and Fenofibrate group(61.65% , 64.37%respectively) than those in Ischemia-reperfusion group(52.33% ) (P<0.05). Conclusion Myocardial ischemia-reperfusion could inducecardiomyocyte apoptosis,and Rosiglitazone and fenofibrate could exertscardioprotective effect against ischemia/reperfusion injury significantlyinhibit cardiomyocyte apoptosis induced by ischemia-reperfusion inrats.Rosiglitazone and Fenofibrat inhibited cardiomyocyte apoptosisprobably by (1)enhancing antioxidant capacity ;(2)inhibiting expressionof NF-κB gene ;(3)inhibiting expression of pro-apoptotic Bax gene andraising the protein expression rations of Bcl-2/Bax.
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