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Trimetazine Preconditoning on Ischemia-Reperfusion Injury in Rats Inhibits Myocardial Apoptosis and Investigates Its Possible Mechanism

Author: XiongGuo
Tutor: MaKangHua
School: Chongqing Medical University
Course: Internal Medicine
Keywords: ischemia/reperfusion apoptosis trimetazidine CREB Bcl-2 Caspase-3
CLC: R965
Type: Master's thesis
Year: 2011
Downloads: 34
Quote: 0
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Abstract


Objective: The aim of this study was to investigate the effects of myocardial apoptosis of trimetazidine preconditioning on heart ischemia-reperfusion injury in rats and its possible mechanism。Methods: Sprague-Dawley male rats were randomly divided into three groups: sham、control and treated groups (n=10)。(1) Sham group, rats without ischemia-reperfusion (I/R), (2) Ischemia/reperfusion (I/R group :NS was fed for 2 weeks to treated animals before the procedure); (3) (I/R+T group: Trimetazidine 10 mg.kg-1.d-1+NS was fed for 2 weeks to treated animals before the procedure)。ischemia-reperfusion experimental models :The rats were subjected to a 45-min left anterior descending coronary artery ischemia followed by a 180-min reperfusion except S group。TUNEL method for cardiomyocyte apoptosis of all groups ;immunohistochemisty for p-CREB expression,immunofluorescence for expressions of Bcl-2 and Caspase3;RT-PCR for expressions of CREB mRNA、Bcl-2 mRNA and Caspase-3 mRNA。 Results: S group with little apoptosis,I/R group with large number of apoptosis,T+I/R group had a significantly lower apoptotic index than I/R group(31.1±0.050 VS 45.5±0.055,P<0·05), but still higher apoptotic index than S group(31.1±0.050 VS 2.70±0.021)。p-CREB、bcl-2 and caspase-3 in S group had the expression of basal level,crebmRNA with no significant differences in all groups (P>0.05),I/R group with a little increase in the p-CREB than S group(P>0·05),I/R group showed a significant increase in caspase-3 levels than both S group and I/R+ T group(P<0·05);I/R+ T group had significant increase in the p-CREB than that both S group and I/R group(P<0·05),and significantly increased the bcl-2 levels and apparently decreased the Caspase-3 levels between protein and mRNA than I/R group(P<0·05),but higher than S group(P<0·05)。Conclusion: trimetazidine preconditioning on heart ischemia-reperfusion in rats apparently inhibits myocardial apoptosis ,and its possible mechanism activation CREB,up-regulation the expressions of p-CREB and Bcl-2,and down- regulation Caspase3。

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