The Effect Of Trimetazidine Post-conditoning On Myocardial Cell Apoptosis In Acute Ischemia-reperfusion Injury Of Rat

ObjectiveTo Investigate the effect of Trimetazidine post-conditoning on myocardial cellapoptosis in acute ischemia-reperfusion injury of rat.MethodsThe40Wistar rats were randomly divided into four groups by weight, with10rats for each group:⑴Sham-operated group: After open chest, cardiac left anterior descendingcoronary artery was only weared needle but not sealed.⑵Ischemia-reperfusion group: Ligate the left anterior descending coronaryartery after chest opening, resulting in ischemia of30min; then loosen theligature to recover the left coronary flow for120min.⑶Trimetazidine group: Intragastric administration of10mg/kg trimetazidinewas given before48h,24h and60min of reperfusion, ascertain peak of bloodconcentration.⑷Ischemic post-conditioning group: Ligate LAD for30min ischemia,then gowith three times circulation of reperfusion for30s and ischemia for30s, andafter that a120min reperfusion was given again.Except for trimetazidine group,the other groups were filled the stomach thesame volume physiological saline in the same time with trimetazidine group.The rat abdominal aorta blood was taken for each group, and after standing andcentrifugation, the supernatant was taken to measure the concentration of serumsample of IL-6and TNF-α through the method of kit，and adopt double sandwichenzyme-linked immunosorbent method; The rats of each group were dissected forheart after taken blood. The myocardial tissue of junction area between infarction areaand normal area was taken to observe the apoptotic myocardial cells ultrastructureusing electronic microscope. Randomly selected five rat hearts were cut into4mm thick slice below ligature.Then detect the apoptotic myocardial cells using Opticalmicroscope with the method of TUNEL,and analyze the grey level through software.The myocardial tissues of left ventricular myocardial cross-sections of the other fiverat hearts below ligature were taken to detect the expression of Bcl-2/Bax mRNAusing RT-qPCR.ResultsCompared with ischemia-reperfusion group, The level of IL-6、TNF-α of theTrimetazidine group and the ischemic post-conditioning group was significantlyreduced (P＜0.05, P＜0.05); The degree of cell nucleus abnormity,cardiac musclefiber injury and mitochondrial swelling and vacuolation of both the two conditioninggroup were obviously alleviated when observing the apoptotic myocardial cells withelectron microscope，so there is a great improvement on the structural damage of theapoptotic myocardial cells,especially the damage of mitochondria; The amount of theapoptotic myocardial cells of both the two conditioning group was significantlyreduced (P＜0.05, P＜0.05); The expression of Bcl-2mRNA of both the twoconditioning group were increased, while the situation of Bax mRNA is opposite (P＜0.05, P＜0.05). The difference between the Trimetazidine group and the post-condition group were not sharp(P＞0.05).ConclusionTMZ post-conditioning not only has the role of anti-MIRI but also anti-apoptosis,and the mechanisms may partly be stabilizing mitochondrial structure, decreasing theproduction of inflammatory cytokines IL-6、TNF-α and disturbing the expression ofBcl-2/Bax mRNA.