| Objective: Inflammatory responses is one of the mechanisms leading to myocardial ischemia-reperfusion injury, a lot of researches indicate that anticytokine therapy can alleviate ischemia-reperfusion injury, TNF-αis one of the most important proinflammatory cytokines, Recombinant Human Tumor Necrosis Factor-αReceptorⅡ:IgG Fc Fusion Protein (rhTNFR:Fc) could combine with TNF-αand inhibit its activity, The latest researches proved Ischaemic postconditioning could reduce the generation of plasma TNF-αat translation level during ischemia-reperfusion. To study whether rhTNFR:Fc combination with ischemic postcondition on the prevention of myocardium ischemia/reperfusion injury is more effectively than monotherapy in vivo rat models of ischemia/reperfusion myocardial.Methods: Fourty eight SD rats were randomly divided into four groups(n=12), all the in vivo rat model of myocardial ischemia-reperfusion were subjected 1 hour of LAD occlusion followed by 6 hours of reperfusion,①In Control group, no interventions were applied;②In rhTNFR:Fc group, rhTNFR:Fc solution (2ml/kg, 1mg/ml) was administered intravenouslly at 30 minutes after ischemia;③In Postcon group:three cycles of 10 seconds of reperfusion and 10 seconds of reocclusion was applied immediately at the onset of reperfusion,④In combination therapy group, rhTNFR:Fc solution (2ml/kg, 1mg/ml) was administered intravenouslly at 30 minutes after ischemia, and three cycles of 10 seconds of reperfusion and 10 seconds of reocclusion was applied immediately at the onset of reperfusion. The plasma TNF-αat different time (0 minute, 30 minutes, 1 hours, 3 hours, 6 hours after reperfusion) were measured by ELISA, at the end of reperfusion, rats were executed, plasma CK-MB and LDH were measured by automatic biochemistry analyzer,myocardial infarct size was determined by Evans blue and TTC staining, the activity of Caspase-3, Bcl-2 at ischemic myocardium were examined by Western blot analysis, apoptotic myocytes at ischemic myocardium were detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), apoptosis index were calculated.Results: RhTNFR:Fc, ischemic postcondition, both combined reduced the plasma LDH, CK-MB, TNF-αlevels (30 minutes,1 hours.,3 hours,6 hours after reperfusion), infarct area, apoptotic myocytes, Caspase-3 expression, increased Bcl-2 expression when compared with controls (P<0.01), ischemic postcondition reduced the plasma TNF-αmore significantly than rhTNFR:Fc at 30min and 1 hour after reperfusion (P<0.01). However, at 0 hour, 3 hours and 6 hours after reperfusion, rhTNFR:Fc reduced the plasma TNF-αmore significantly(P<0.01).Conclusions: Both rhTNFR:Fc and ischemic postcondion could inhibit TNF-αactivity during ischemia-reperfusion period, attenuate myocyte apoptosis, reduce infarction, in respect of inhibiting TNF-α, rhTNFR:Fc effects slowly but lastingly, Ischaemic postcondition effects transiently but instantly, there is a additive effect when both used in comibinetion. |
